VCV000374027.45 - ClinVar

NM_019098.5(CNGB3):c.819_826del (p.Arg274fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(16)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_019098.5(CNGB3):c.819_826del (p.Arg274fs)

Variation ID: 374027 Accession: VCV000374027.45

Type and length

Deletion, 8 bp

Location

Cytogenetic: 8q21.3 8: 86666951-86666958 (GRCh38) [ NCBI UCSC ] 8: 87679179-87679186 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 16, 2017	Oct 20, 2024	Jan 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_019098.5:c.819_826del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_061971.3:p.Arg274fs	frameshift
NM_019098.4:c.819_826delCAGACTCC
NC_000008.11:g.86666953_86666960del
NC_000008.10:g.87679181_87679188del
NG_016980.1:g.81718_81725del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000008.11:86666950:GGAGTCTGGG:GG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 605080.0003 dbSNP: rs775796581 ClinGen: CA4800270 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CNGB3		-	-	GRCh38 GRCh37	1235	1279

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Abnormal electroretinogram Nystagmus	Pathogenic (1)	criteria provided, single submitter	Jul 11, 2014	RCV000415035.3
Leber congenital amaurosis	Pathogenic (2)	no assertion criteria provided	Sep 1, 2016	RCV000504685.4
Achromatopsia 3	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	Sep 23, 2022	RCV000498183.7
Achromatopsia	Pathogenic (2)	criteria provided, single submitter	Mar 20, 2018	RCV000592388.3
not provided	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	Jan 29, 2024	RCV000727187.34
Retinal dystrophy	Pathogenic (1)	criteria provided, single submitter	Jun 18, 2019	RCV001074298.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jul 11, 2014)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Abnormal electroretinogram Nystagmus Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000492719.1 First in ClinVar: Jan 16, 2017 Last updated: Jan 16, 2017
Pathogenic (Sep 03, 2015)	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)) Method: clinical testing	Achromatopsia 3 Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000678190.1 First in ClinVar: Jan 06, 2018 Last updated: Jan 06, 2018	Publications: PubMed (4) PubMed: 15712225‚ 15657609‚ 17652762‚ 10888875
Pathogenic (Mar 20, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Achromatopsia Affected status: yes Allele origin: germline	Molecular Genetics Laboratory, Institute for Ophthalmic Research Accession: SCV000700210.1 First in ClinVar: Apr 02, 2018 Last updated: Apr 02, 2018
Pathogenic (Feb 20, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000706474.2 First in ClinVar: Dec 15, 2018 Last updated: Dec 15, 2018	Publications: PubMed (1) PubMed: 25558176 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CNGB3 Number of individuals with the variant: 1 Sex: mixed
Pathogenic (Jun 18, 2019)	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme) Method: clinical testing	Retinal dystrophy Affected status: yes Allele origin: germline	Blueprint Genetics Accession: SCV001239871.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 Comment: My Retina Tracker patient
Pathogenic (Jan 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Achromatopsia 3 Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001368242.2 First in ClinVar: Jul 06, 2020 Last updated: Dec 12, 2020	Comment: This variant was classified as: Pathogenic.
Pathogenic (Jun 17, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV001762189.1 First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021	Clinical Features: Parkinsonian disorder (present) Sex: female
Pathogenic (Sep 23, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Achromatopsia 3 Affected status: yes Allele origin: germline	Laboratory of Medical Genetics, National & Kapodistrian University of Athens Accession: SCV002577447.1 First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022	Comment: PVS1, PM2, PP5
Pathogenic (Jul 05, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV004012353.1 First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023	Comment: Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more) Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25558176, 17652762, 15657609, 22975760, 20079539, 10888875, 28795510, 28041643, 15712225, 30418171, 32581362, 33807868, 34426522, 32531858, 34449556, 29769798) (less)
Pathogenic (Jan 29, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000959880.6 First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024	Publications: PubMed (4) PubMed: 28795510‚ 10888875‚ 20079539‚ 29769798 Comment: This sequence change creates a premature translational stop signal (p.Arg274Valfs13) in the CNGB3 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Arg274Valfs13) in the CNGB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 28795510). This variant is present in population databases (rs775796581, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with achromatopsia or an inherited retinal dystrophy (PMID: 10888875, 20079539, 29769798). This variant is also known as Pro160 del8bp, c.819_826del8. ClinVar contains an entry for this variant (Variation ID: 374027). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Dec 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001245905.25 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Comment: CNGB3: PVS1, PM3:Strong, PM2 Number of individuals with the variant: 5
Pathogenic (Mar 27, 2017)	no assertion criteria provided Method: research	ACHM3 Affected status: yes Allele origin: germline	Molecular Genetics Laboratory, Institute for Ophthalmic Research Accession: SCV000575785.1 First in ClinVar: Aug 20, 2017 Last updated: Aug 20, 2017	Publications: PubMed (1) PubMed: 28795510
Pathogenic (Jan 01, 2015)	no assertion criteria provided Method: research	Leber congenital amaurosis Affected status: yes Allele origin: unknown	NIHR Bioresource Rare Diseases, University of Cambridge Accession: SCV000598866.1 First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017	Publications: PubMed (2) PubMed: 28041643‚ 10888875 Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: European
Pathogenic (Sep 01, 2016)	no assertion criteria provided Method: clinical testing	Leber congenital amaurosis Affected status: yes Allele origin: unknown	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Accession: SCV000804626.2 First in ClinVar: Sep 10, 2018 Last updated: Sep 10, 2018	Number of individuals with the variant: 1
Pathogenic (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Achromatopsia Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001454553.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Pathogenic (Jul 01, 2000)	no assertion criteria provided Method: literature only	ACHROMATOPSIA 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000025719.4 First in ClinVar: Apr 04, 2013 Last updated: Oct 08, 2024	Publications: PubMed (1) PubMed: 10888875 Comment on evidence: For discussion of the 8-bp deletion (c.819del8) in the CNGB3 gene that was found in compound heterozygous state in Pingelapese brothers with achromatopsia (ACHM3; 262300) … (more) For discussion of the 8-bp deletion (c.819del8) in the CNGB3 gene that was found in compound heterozygous state in Pingelapese brothers with achromatopsia (ACHM3; 262300) by Sundin et al. (2000), see 605080.0002. (less)
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Comment:

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25558176, 17652762, 15657609, 22975760, 20079539, 10888875, 28795510, 28041643, 15712225, 30418171, 32581362, 33807868, 34426522, 32531858, 34449556, 29769798)

Comment:

This sequence change creates a premature translational stop signal (p.Arg274Valfs*13) in the CNGB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 28795510). This variant is present in population databases (rs775796581, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with achromatopsia or an inherited retinal dystrophy (PMID: 10888875, 20079539, 29769798). This variant is also known as Pro160 del8bp, c.819_826del8. ClinVar contains an entry for this variant (Variation ID: 374027). For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Novel variants identified with next-generation sequencing in Polish patients with cone-rod dystrophy.	Wawrocka A	Molecular vision	2018	PMID: 29769798
CNGB3 mutation spectrum including copy number variations in 552 achromatopsia patients.	Mayer AK	Human mutation	2017	PMID: 28795510
Five novel CNGB3 gene mutations in Polish patients with achromatopsia.	Wawrocka A	Molecular vision	2014	PMID: 25558176
Comprehensive analysis of the achromatopsia genes CNGA3 and CNGB3 in progressive cone dystrophy.	Thiadens AA	Ophthalmology	2010	PMID: 20079539
CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function.	Khan NW	Investigative ophthalmology & visual science	2007	PMID: 17652762
Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases.	Nishiguchi KM	Human mutation	2005	PMID: 15712225
CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.	Kohl S	European journal of human genetics : EJHG	2005	PMID: 15657609
Genetic basis of total colourblindness among the Pingelapese islanders.	Sundin OH	Nature genetics	2000	PMID: 10888875
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CNGB3	-	-	-	-

Text-mined citations for rs775796581 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_019098.5(CNGB3):c.819_826del (p.Arg274fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs775796581 ...