Genetic Variant BHLHE41:p.Ala360Ala (chr12-26122435-G-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_030762.3(BHLHE41):c.1080C>G(p.Ala360Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,354,708 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00040 ( 2 hom. )

Consequence

BHLHE41
NM_030762.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.322

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 12-26122435-G-C is Benign according to our data. Variant chr12-26122435-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 712110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.322 with no splicing effect.

BS2

High AC in GnomAd4 at 69 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030762.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHLHE41	NM_030762.3	MANE Select	c.1080C>G	p.Ala360Ala	synonymous	Exon 5 of 5	NP_110389.1	Q9C0J9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BHLHE41	ENST00000242728.5	TSL:1 MANE Select	c.1080C>G	p.Ala360Ala	synonymous	Exon 5 of 5	ENSP00000242728.4	Q9C0J9
BHLHE41	ENST00000957109.1		c.1086C>G	p.Ala362Ala	synonymous	Exon 5 of 5	ENSP00000627168.1
SSPN	ENST00000538142.5	TSL:4	c.-31+283G>C		intron	N/A	ENSP00000445360.1	F5H381

Frequencies

GnomAD3 genomes

AF:

0.000464

AC:

AN:

148774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.000400

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000434

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000472

AC:

AN:

78338

AF XY:

0.000509

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000456

Gnomad ASJ exome

AF:

0.000170

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000655

Gnomad OTH exome

AF:

0.000975

GnomAD4 exome

AF:

0.000400

AC:

482

AN:

1205826

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

264

AN XY:

592478

show subpopulations

African (AFR)

AF:

0.0000405

AC:

AN:

24692

American (AMR)

AF:

0.000404

AC:

AN:

22302

Ashkenazi Jewish (ASJ)

AF:

0.0000523

AC:

AN:

19104

East Asian (EAS)

AF:

0.00

AC:

AN:

25508

South Asian (SAS)

AF:

0.000342

AC:

AN:

55498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31210

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

3830

European-Non Finnish (NFE)

AF:

0.000423

AC:

413

AN:

976432

Other (OTH)

AF:

0.000614

AC:

AN:

47250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000463

AC:

AN:

148882

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

AN XY:

72636

show subpopulations

African (AFR)

AF:

0.0000972

AC:

AN:

41170

American (AMR)

AF:

0.000399

AC:

AN:

15026

Ashkenazi Jewish (ASJ)

AF:

0.000293

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5070

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9354

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000434

AC:

AN:

66752

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000552

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.4

(source)

DANN

Benign

0.51

PhyloP100

-0.32

PromoterAI

0.23

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over