rs4757142

Variant names:

• chr11-13304148-G-A
• rs4757142
• NM_001297719.2:c.-262-5839G>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.-262-5839G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,848 control chromosomes in the GnomAD database, including 18,796 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 0.48 (18796 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-262-5839G>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.-262-5839G>A		intron_variant	Intron 1 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72122 AN: 151730 Hom.: 18792 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.475 AC: 72148 AN: 151848 Hom.: 18796 Cov.: 31 AF XY: 0.474 AC XY: 35190 AN XY: 74176

African (AFR) AF: 0.252 AC: 10411 AN: 41390

American (AMR) AF: 0.498 AC: 7606 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1884 AN: 3460

East Asian (EAS) AF: 0.413 AC: 2116 AN: 5128

South Asian (SAS) AF: 0.470 AC: 2262 AN: 4808

European-Finnish (FIN) AF: 0.568 AC: 5977 AN: 10520

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40308 AN: 67966

Other (OTH) AF: 0.504 AC: 1064 AN: 2112

Alfa AF: 0.545 Hom.: 11069

Bravo AF: 0.461

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.66
PhyloP100		-0.022
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: rs4757142; hg19: chr11-13325695;