NM_001297719.2:c.-262-210G>A

Variant names:

• chr11-13309777-G-A
• rs4757145
• NM_001297719.2:c.-262-210G>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.-262-210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,822 control chromosomes in the GnomAD database, including 14,267 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 0.43 (14267 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-262-210G>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.-262-210G>A		intron_variant	Intron 1 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65591 AN: 151704 Hom.: 14256 Cov.: 31

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.432 AC: 65654 AN: 151822 Hom.: 14267 Cov.: 31 AF XY: 0.438 AC XY: 32515 AN XY: 74178

African (AFR) AF: 0.448 AC: 18528 AN: 41362

American (AMR) AF: 0.449 AC: 6857 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1480 AN: 3468

East Asian (EAS) AF: 0.584 AC: 3001 AN: 5136

South Asian (SAS) AF: 0.519 AC: 2497 AN: 4812

European-Finnish (FIN) AF: 0.478 AC: 5042 AN: 10546

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26753 AN: 67926

Other (OTH) AF: 0.402 AC: 846 AN: 2104

Alfa AF: 0.398 Hom.: 20469

Bravo AF: 0.428

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		0.39
PromoterAI		-0.016	Neutral
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: rs4757145; hg19: chr11-13331324; COSMIC: COSV62987846; COSMIC: COSV62987846;