rs7950226

Variant names:

• chr11-13296592-G-A
• rs7950226
• NM_001297719.2:c.-262-13395G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):​c.-262-13395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,056 control chromosomes in the GnomAD database, including 13,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13912 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-262-13395G>A		intron_variant	Intron 1 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-262-13395G>A		intron_variant	Intron 1 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61273 AN: 151938 Hom.: 13898 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 61298 AN: 152056 Hom.: 13912 Cov.: 33 AF XY: 0.407 AC XY: 30221 AN XY: 74312

African (AFR) AF: 0.188 AC: 7785 AN: 41484

American (AMR) AF: 0.515 AC: 7882 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3117 AN: 5176

South Asian (SAS) AF: 0.478 AC: 2305 AN: 4818

European-Finnish (FIN) AF: 0.439 AC: 4636 AN: 10552

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32873 AN: 67942

Other (OTH) AF: 0.391 AC: 824 AN: 2110

Alfa AF: 0.456 Hom.: 30443

Bravo AF: 0.399

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.028
DANN	Benign	0.63
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7950226; hg19: chr11-13318139;