VCV000198079.39 - ClinVar

NM_000414.4(HSD17B4):c.317G>A (p.Arg106His)

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.

(14)

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.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000414.4(HSD17B4):c.317G>A (p.Arg106His)

Variation ID: 198079 Accession: VCV000198079.39

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q23.1 5: 119475838 (GRCh38) [ NCBI UCSC ] 5: 118811533 (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	Oct 2, 2016	Feb 28, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000414.4:c.317G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000405.1:p.Arg106His	missense
NM_001199291.3:c.392G>A	NP_001186220.1:p.Arg131His	missense
NM_001199292.2:c.263G>A	NP_001186221.1:p.Arg88His	missense
NM_001292027.2:c.245G>A	NP_001278956.1:p.Arg82His	missense
NM_001292028.2:c.-95G>A		5 prime UTR
NM_001374497.1:c.317G>A	NP_001361426.1:p.Arg106His	missense
NM_001374498.1:c.317G>A	NP_001361427.1:p.Arg106His	missense
NM_001374499.1:c.22+111G>A		intron variant
NM_001374500.1:c.-222G>A		5 prime UTR
NM_001374501.1:c.-95G>A		5 prime UTR
NM_001374502.1:c.-95G>A		5 prime UTR
NM_001374503.1:c.-95G>A		5 prime UTR
NR_164653.1:n.396G>A		non-coding transcript variant
NR_164654.1:n.584G>A		non-coding transcript variant
NC_000005.10:g.119475838G>A
NC_000005.9:g.118811533G>A
NG_008182.1:g.28386G>A
	P51659:p.Arg106His

... more HGVS ... less HGVS

Protein change

R106H, R131H, R82H, R88H

Other names

Canonical SPDI

NC_000005.10:119475837:G:A

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.

0.36262 (A)

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

1000 Genomes Project 30x 0.35509

1000 Genomes Project 0.36262

Trans-Omics for Precision Medicine (TOPMed) 0.37967

The Genome Aggregation Database (gnomAD) 0.38375

Exome Aggregation Consortium (ExAC) 0.44004

The Genome Aggregation Database (gnomAD), exomes 0.45087

Links

dbSNP: rs25640 ClinGen: CA203225 UniProtKB: P51659#VAR_014872 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.
HSD17B4		-	-	GRCh38 GRCh37	1294	1350

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.
not specified	Benign (6)	criteria provided, multiple submitters, no conflicts	May 9, 2017	RCV000179310.28
Bifunctional peroxisomal enzyme deficiency	Benign (3)	criteria provided, multiple submitters, no conflicts	Jul 10, 2021	RCV000391832.16
Perrault syndrome 1	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 10, 2021	RCV000362861.15
not provided	Benign (2)	criteria provided, single submitter	Nov 29, 2023	RCV000676075.22
Bifunctional peroxisomal enzyme deficiency Perrault syndrome	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV001517001.15

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.
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000304079.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jan 16, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000231540.5 First in ClinVar: Jun 28, 2015 Last updated: Apr 09, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HSD17B4 Number of individuals with the variant: 2 Zygosity: Homozygote, Single Heterozygote Sex: mixed
Benign (Oct 31, 2014)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000269165.2 First in ClinVar: May 29, 2016 Last updated: Apr 09, 2018	Comment: Arg131His in exon 7 of HSD17B4: This variant is not expected to have clinical si gnificance because it has been identified in 46% (3954/8596) of … (more) Arg131His in exon 7 of HSD17B4: This variant is not expected to have clinical si gnificance because it has been identified in 46% (3954/8596) of European America n chromosomes and 18% (776/4404) of African American chromosomes by the NHLBI Ex ome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs25640). (less) Number of individuals with the variant: 665
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Perrault syndrome 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000452107.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Bifunctional peroxisomal enzyme deficiency Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000452108.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
Benign (Nov 29, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001158876.8 First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024
Benign (May 09, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000728564.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Jul 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Bifunctional peroxisomal enzyme deficiency Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001762860.1 First in ClinVar: Aug 05, 2021 Last updated: Aug 05, 2021	Sex: mixed
Benign (Jul 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Perrault syndrome 1 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001762861.1 First in ClinVar: Aug 05, 2021 Last updated: Aug 05, 2021	Sex: mixed
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Perrault syndrome Bifunctional peroxisomal enzyme deficiency Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001725385.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024
Benign (Oct 26, 2015)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801810.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001741765.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Benign (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Bifunctional peroxisomal enzyme deficiency Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001457634.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001953418.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

Arg131His in exon 7 of HSD17B4: This variant is not expected to have clinical si gnificance because it has been identified in 46% (3954/8596) of European America n chromosomes and 18% (776/4404) of African American chromosomes by the NHLBI Ex ome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs25640).

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HSD17B4	-	-	-	-

Text-mined citations for rs25640 ...

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 Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NM_000414.4(HSD17B4):c.317G>A (p.Arg106His)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs25640 ...