rs4757151

Variant names:

• chr11-13370666-A-G
• rs4757151
• NM_001297719.2:c.820+899A>G

Variant summary

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

The NM_001297719.2(BMAL1):​c.820+899A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,062 control chromosomes in the GnomAD database, including 15,813 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 0.44 (15813 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.820+899A>G		intron_variant	Intron 12 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.820+899A>G		intron_variant	Intron 12 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66443 AN: 151944 Hom.: 15806 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.437 AC: 66478 AN: 152062 Hom.: 15813 Cov.: 32 AF XY: 0.441 AC XY: 32764 AN XY: 74300

African (AFR) AF: 0.234 AC: 9717 AN: 41514

American (AMR) AF: 0.491 AC: 7499 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1961 AN: 5156

South Asian (SAS) AF: 0.539 AC: 2595 AN: 4812

European-Finnish (FIN) AF: 0.550 AC: 5815 AN: 10572

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35583 AN: 67950

Other (OTH) AF: 0.467 AC: 983 AN: 2106

Alfa AF: 0.495 Hom.: 24715

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.82
DANN	Benign	0.42
PhyloP100		-0.58
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: rs4757151; hg19: chr11-13392213;