VCV000691289.3 - ClinVar

NM_030762.3(BHLHE41):c.1084T>C (p.Tyr362His)

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.

(1)

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.

Affects

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_030762.3(BHLHE41):c.1084T>C (p.Tyr362His)

Variation ID: 691289 Accession: VCV000691289.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12p12.1 12: 26122431 (GRCh38) [ NCBI UCSC ] 12: 26275364 (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	Mar 26, 2020	Mar 26, 2020	Mar 17, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_030762.3:c.1084T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_110389.1:p.Tyr362His	missense
NC_000012.12:g.26122431A>G
NC_000012.11:g.26275364A>G
NG_012011.2:g.5441A>G
NG_021173.1:g.7640T>C
LRG_209:g.5441A>G

... more HGVS ... less HGVS

Protein change

Y362H

Other names

Canonical SPDI

NC_000012.12:26122430:A:G

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.

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Links

OMIM: 606200.0002 dbSNP: rs1591838266 VarSome

Comment on variant

NCBI staff established the location of this variant from the trace in Figure S1 in the paper by Pellegrino et al., 2014 (PubMed 25083013).

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.
BHLHE41		-	-	GRCh38 GRCh37	-	85
SSPN		-	-	GRCh38 GRCh37	9	112

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.
Short sleep, familial natural, 1	Affects (1)	no assertion criteria provided	Mar 17, 2020	RCV000851542.3

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.
Affects (Mar 17, 2020)	no assertion criteria provided Method: literature only	SHORT SLEEP, FAMILIAL NATURAL, 1 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000994614.2 First in ClinVar: Sep 29, 2019 Last updated: Mar 26, 2020	Publications: PubMed (1) PubMed: 25083013 Comment on evidence: In a 27-year-old African American man with familial natural short sleep-1 (FNSS1; 612975) who also demonstrated resistance to sleep deprivation, Pellegrino et al. (2014) identified … (more) In a 27-year-old African American man with familial natural short sleep-1 (FNSS1; 612975) who also demonstrated resistance to sleep deprivation, Pellegrino et al. (2014) identified a heterozygous c.1084T-C transition in exon 5 of the BHLHE41 gene, resulting in a tyr362-to-his (Y362H) substitution. The variant, which was found by Sanger sequencing, was not found in the individual's unaffected dizygotic twin brother, who did not manifest the phenotype. The average sleep duration in the affected twin was 299.3 minutes, compared to the unaffected twin, which was 364.7 minutes. Following sleep deprivation, the affected twin had fewer performance lapses compared to the unaffected twin. In vitro functional expression studies in HEK293 cells showed that the BHLHE41 variant was unable to suppress CLOCK (601851)/BMAL1 (602550) and NPAS2 (603347)/BMAL1 transactivation. Western blot analysis showed protein levels comparable to wildtype. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans.	Pellegrino R	Sleep	2014	PMID: 25083013

Text-mined citations for rs1591838266 ...

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 Aug 06, 2023

ClinVar Genomic variation as it relates to human health

NM_030762.3(BHLHE41):c.1084T>C (p.Tyr362His)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1591838266 ...