Variant chr12-26122222-C-CGCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_SupportingBP6BS2

The NM_030762.3(BHLHE41):c.1290_1292dupCGC(p.Ala431dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.000484 in 1,302,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

BHLHE41
NM_030762.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.13

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 Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_030762.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 12-26122222-C-CGCG is Benign according to our data. Variant chr12-26122222-C-CGCG is described in ClinVar as [Likely_benign]. Clinvar id is 3046119.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BHLHE41	NM_030762.3 link	c.1290_1292dupCGC	p.Ala431dup	disruptive_inframe_insertion	Exon 5 of 5	ENST00000242728.5	NP_110389.1	Q9C0J9Q8TAT1A0A024RAV8
SSPN	XM_011520853.4 link	c.-31+80_-31+82dupGCG		intron_variant	Intron 1 of 2		XP_011519155.1	Q14714-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BHLHE41	ENST00000242728.5 link	c.1290_1292dupCGC	p.Ala431dup	disruptive_inframe_insertion	Exon 5 of 5	1	NM_030762.3	ENSP00000242728.4	Q9C0J9
SSPN	ENST00000538142.5 link	c.-31+80_-31+82dupGCG		intron_variant	Intron 1 of 2	4		ENSP00000445360.1	F5H381
SSPN	ENST00000534829.5 link	n.101+80_101+82dupGCG		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.000518

AC:

AN:

150464

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000707

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000982

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000399

Gnomad OTH

AF:

0.00194

GnomAD4 exome

AF:

0.000479

AC:

552

AN:

1151440

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

278

AN XY:

554154

show subpopulations

Gnomad4 AFR exome

AF:

0.000261

Gnomad4 AMR exome

AF:

0.000578

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000377

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000280

Gnomad4 NFE exome

AF:

0.000549

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000518

AC:

AN:

150570

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

AN XY:

73512

show subpopulations

Gnomad4 AFR

AF:

0.000705

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000982

Gnomad4 NFE

AF:

0.000400

Gnomad4 OTH

AF:

0.00192

Alfa

AF:

0.000498

Hom.:

Asia WGS

AF:

0.000291

AC:

AN:

3452

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BHLHE41-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2023

This variant is classified as likely 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

Splicing

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