rs4757144

Variant names:

• chr11-13309679-G-A
• rs4757144
• NM_001297719.2:c.-262-308G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-13309679-G-A
• chr11-13309679-G-C
• chr11-13309679-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):​c.-262-308G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,874 control chromosomes in the GnomAD database, including 16,495 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 0.42 (16495 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-262-308G>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.-262-308G>A		intron_variant	Intron 1 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64472 AN: 151756 Hom.: 16493 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.425 AC: 64485 AN: 151874 Hom.: 16495 Cov.: 31 AF XY: 0.422 AC XY: 31312 AN XY: 74214

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.473

Alfa AF: 0.549 Hom.: 27748

Bravo AF: 0.413

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.9
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs4757144; hg19: chr11-13331226;