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. The variant received -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
• Publications: 42 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297719.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	NM_001297719.2	MANE Select	c.-262-308G>A		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.-207-308G>A		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-262-308G>A		intron	N/A	NP_001338743.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	ENST00000403290.6	TSL:1 MANE Select	c.-262-308G>A		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.-262-308G>A		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000401424.6	TSL:1	c.-407-308G>A		intron	N/A	ENSP00000385915.2	O00327-9

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

African (AFR) AF: 0.123 AC: 5112 AN: 41410

American (AMR) AF: 0.480 AC: 7322 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2125 AN: 5148

South Asian (SAS) AF: 0.455 AC: 2192 AN: 4818

European-Finnish (FIN) AF: 0.496 AC: 5226 AN: 10530

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.577 AC: 39168 AN: 67932

Other (OTH) AF: 0.473 AC: 1000 AN: 2112

Alfa AF: 0.505 Hom.: 39651

Bravo AF: 0.413

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.9
DANN	Benign	0.81
PhyloP100		-0.13
PromoterAI		0.0031	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: rs4757144; hg19: chr11-13331226;