Variant 12-26122399-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_030762.3(BHLHE41):c.1116G>C(p.Leu372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,283,514 control chromosomes in the GnomAD database, including 772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.023 ( 59 hom., cov: 30)

Exomes 𝑓: 0.033 ( 713 hom. )

Consequence

BHLHE41
NM_030762.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

BHLHE41 (HGNC:16617): (basic helix-loop-helix family member e41) This gene encodes a basic helix-loop-helix protein expressed in various tissues. The encoded protein can interact with ARNTL or compete for E-box binding sites in the promoter of PER1 and repress CLOCK/ARNTL's transactivation of PER1. This gene is believed to be involved in the control of circadian rhythm and cell differentiation. Defects in this gene are associated with the short sleep phenotype. [provided by RefSeq, Feb 2014]

BHLHE41 links:

SSPN (HGNC:11322): (sarcospan) This gene encodes a member of the dystrophin-glycoprotein complex (DGC). The DGC spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Two alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

SSPN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 12-26122399-C-G is Benign according to our data. Variant chr12-26122399-C-G is described in ClinVar as [Benign]. Clinvar id is 3055569.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0226 (3357/148408) while in subpopulation AMR AF= 0.0377 (567/15026). AF 95% confidence interval is 0.0352. There are 59 homozygotes in gnomad4. There are 1546 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3357 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHLHE41	NM_030762.3 linkuse as main transcript	c.1116G>C	p.Leu372=	synonymous_variant	5/5	ENST00000242728.5
SSPN	XM_011520853.4 linkuse as main transcript	c.-31+247C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BHLHE41	ENST00000242728.5 linkuse as main transcript	c.1116G>C	p.Leu372=	synonymous_variant	5/5	1	NM_030762.3	P1
SSPN	ENST00000538142.5 linkuse as main transcript	c.-31+247C>G		intron_variant		4
SSPN	ENST00000534829.5 linkuse as main transcript	n.101+247C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3359

AN:

148300

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00552

Gnomad AMI

AF:

0.0419

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00479

Gnomad FIN

AF:

0.00770

Gnomad MID

AF:

0.0160

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0424

GnomAD3 exomes

AF:

0.0232

AC:

1514

AN:

65158

Hom.:

AF XY:

0.0215

AC XY:

820

AN XY:

38152

show subpopulations

Gnomad AFR exome

AF:

0.00414

Gnomad AMR exome

AF:

0.0237

Gnomad ASJ exome

AF:

0.0369

Gnomad EAS exome

AF:

0.000482

Gnomad SAS exome

AF:

0.00735

Gnomad FIN exome

AF:

0.00675

Gnomad NFE exome

AF:

0.0337

Gnomad OTH exome

AF:

0.0246

GnomAD4 exome

AF:

0.0326

AC:

37036

AN:

1135106

Hom.:

713

Cov.:

AF XY:

0.0324

AC XY:

17889

AN XY:

551768

show subpopulations

Gnomad4 AFR exome

AF:

0.00546

Gnomad4 AMR exome

AF:

0.0266

Gnomad4 ASJ exome

AF:

0.0348

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00653

Gnomad4 FIN exome

AF:

0.00734

Gnomad4 NFE exome

AF:

0.0362

Gnomad4 OTH exome

AF:

0.0279

GnomAD4 genome

AF:

0.0226

AC:

3357

AN:

148408

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1546

AN XY:

72354

show subpopulations

Gnomad4 AFR

AF:

0.00550

Gnomad4 AMR

AF:

0.0377

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00480

Gnomad4 FIN

AF:

0.00770

Gnomad4 NFE

AF:

0.0335

Gnomad4 OTH

AF:

0.0419

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0245

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BHLHE41-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 03, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.7

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over