Variant rs70965442 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000403482.7(BMAL1):c.37G>A(p.Val13Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,585,270 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 22 hom. )

Consequence

BMAL1
ENST00000403482.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.155

Variant links:

Genes affected

BMAL1 (HGNC:701): (basic helix-loop-helix ARNT like 1) The protein encoded by this gene is a basic helix-loop-helix protein that forms a heterodimer with CLOCK. This heterodimer binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Defects in this gene have been linked to infertility, problems with gluconeogenesis and lipogenesis, and altered sleep patterns. The protein regulates interferon-stimulated gene expression and is an important factor in viral infection, including COVID-19. [provided by RefSeq, Oct 2021]

BMAL1 links:

LOC124902636 (HGNC:):

LOC124902636 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063203573).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL1	NM_001297719.2 linkuse as main transcript	c.180-137G>A		intron_variant		ENST00000403290.6	NP_001284648.1
LOC124902636	XR_007062601.1 linkuse as main transcript	n.87-627C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6 linkuse as main transcript	c.180-137G>A		intron_variant		1	NM_001297719.2	ENSP00000384517	P4	O00327-2

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

344

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00343

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00214

AC:

434

AN:

202922

Hom.:

AF XY:

0.00213

AC XY:

232

AN XY:

108960

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000260

Gnomad FIN exome

AF:

0.000253

Gnomad NFE exome

AF:

0.00364

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00440

AC:

6309

AN:

1432944

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

3046

AN XY:

710652

show subpopulations

Gnomad4 AFR exome

AF:

0.000801

Gnomad4 AMR exome

AF:

0.00278

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000108

Gnomad4 FIN exome

AF:

0.000154

Gnomad4 NFE exome

AF:

0.00543

Gnomad4 OTH exome

AF:

0.00334

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152326

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00313

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00343

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00277

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00649

AC:

ExAC

AF:

0.00174

AC:

209

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.1

DANN

Benign

0.95

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.46

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PROVEAN

Benign

0.20

REVEL

Benign

0.024

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.51

Vest4

0.26

MVP

0.25

ClinPred

0.040

GERP RS

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over