NM_033028.5(BBS4):c.864+1G>C AND Bardet-Biedl syndrome 4

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 20, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002227533.4

Allele description [Variation Report for NM_033028.5(BBS4):c.864+1G>C]

NM_033028.5(BBS4):c.864+1G>C

Gene:

BBS4:Bardet-Biedl syndrome 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_033028.5(BBS4):c.864+1G>C

Other names:

NM_033028.5:c.864+1G>C

HGVS:

NC_000015.10:g.72731458G>C
NG_009416.2:g.50274G>C
NG_009416.3:g.50253G>C
NM_001252678.2:c.348+1G>C
NM_001320665.2:c.795+1G>C
NM_033028.5:c.864+1G>CMANE SELECT
NC_000015.9:g.73023799G>C
NM_033028.4:c.864+1G>C

Links:

dbSNP: rs2151047618

NCBI 1000 Genomes Browser:

rs2151047618

Molecular consequence:

NM_001252678.2:c.348+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001320665.2:c.795+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_033028.5:c.864+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Bardet-Biedl syndrome 4 (BBS4)
Identifiers:: MONDO: MONDO:0014433; MedGen: C2936864; Orphanet: 110; OMIM: 615982

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002507055	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 4, 2022)	germline	curation	PubMed (1) [See all records that cite this PMID]
SCV004214103	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 20, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002507055

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 4, 2022)

germline

curation

PubMed (1)
[See all records that cite this PMID]

SCV004214103

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 20, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV002507055.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

The heterozygous c.864+1G>C variant in BBS4 was identified by our study in the compound heterozygous state, along with another likely pathogenic variant, in 1 individual with Bardet-Biedl syndrome 4. The variant has not been previously reported in individuals with Bardet-Biedl syndrome 4 and was absent from large population studies. This variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the BBS4 gene is a moderately established disease mechanism in autosomal recessive Bardet-Biedl syndrome 4. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PVS1_supporting, PM3 (Richards 2015).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004214103.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 30, 2024

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