rs969485

Variant names:

• chr11-13381496-G-A
• rs969485
• NM_001297719.2:c.1617+242G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-13381496-G-A
• chr11-13381496-G-C

Variant summary

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

The NM_001297719.2(BMAL1):​c.1617+242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,110 control chromosomes in the GnomAD database, including 33,229 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 0.65 (33229 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 29 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.1617+242G>A		intron_variant	Intron 18 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.1617+242G>A		intron_variant	Intron 18 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99217 AN: 151992 Hom.: 33212 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.653 AC: 99290 AN: 152110 Hom.: 33229 Cov.: 32 AF XY: 0.657 AC XY: 48845 AN XY: 74386

African (AFR) AF: 0.529 AC: 21947 AN: 41484

American (AMR) AF: 0.665 AC: 10168 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2305 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2194 AN: 5172

South Asian (SAS) AF: 0.758 AC: 3652 AN: 4818

European-Finnish (FIN) AF: 0.806 AC: 8547 AN: 10604

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48401 AN: 67966

Other (OTH) AF: 0.647 AC: 1363 AN: 2108

Alfa AF: 0.690 Hom.: 149872

Bravo AF: 0.633

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.17
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: rs969485; hg19: chr11-13403043;