rs9633835

Variant names:

• chr11-13324046-G-A
• rs9633835
• NM_001297719.2:c.-189-2367G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-13324046-G-A
• chr11-13324046-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.-189-2367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,962 control chromosomes in the GnomAD database, including 12,570 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 0.41 (12570 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 17 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-189-2367G>A		intron_variant	Intron 2 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-189-2367G>A		intron_variant	Intron 2 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61665 AN: 151844 Hom.: 12567 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.406 AC: 61700 AN: 151962 Hom.: 12570 Cov.: 32 AF XY: 0.410 AC XY: 30464 AN XY: 74292

African (AFR) AF: 0.405 AC: 16787 AN: 41420

American (AMR) AF: 0.430 AC: 6581 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3472

East Asian (EAS) AF: 0.568 AC: 2932 AN: 5162

South Asian (SAS) AF: 0.513 AC: 2472 AN: 4822

European-Finnish (FIN) AF: 0.406 AC: 4279 AN: 10548

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25774 AN: 67938

Other (OTH) AF: 0.385 AC: 813 AN: 2110

Alfa AF: 0.382 Hom.: 5281

Bravo AF: 0.404

Asia WGS AF: 0.511 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.11
PhyloP100		-0.88
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: rs9633835; hg19: chr11-13345593;