11-13334483-A-G

Variant names:

• chr11-13334483-A-G
• rs7947951
• NM_001297719.2:c.-135+8016A>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.-135+8016A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,792 control chromosomes in the GnomAD database, including 34,233 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 0.66 (34233 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 21 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 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.-135+8016A>G		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.-134-15462A>G		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-135+8016A>G		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.-135+8016A>G		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.-135+8016A>G		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000401424.6	TSL:1	c.-334-15462A>G		intron	N/A	ENSP00000385915.2	O00327-9

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100716 AN: 151676 Hom.: 34181 Cov.: 31

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.664 AC: 100831 AN: 151792 Hom.: 34233 Cov.: 31 AF XY: 0.653 AC XY: 48455 AN XY: 74156

African (AFR) AF: 0.757 AC: 31324 AN: 41376

American (AMR) AF: 0.616 AC: 9416 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1703 AN: 5162

South Asian (SAS) AF: 0.551 AC: 2646 AN: 4806

European-Finnish (FIN) AF: 0.525 AC: 5489 AN: 10452

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.679 AC: 46103 AN: 67940

Other (OTH) AF: 0.674 AC: 1420 AN: 2108

Alfa AF: 0.662 Hom.: 13686

Bravo AF: 0.677

Asia WGS AF: 0.463 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.67
PhyloP100		-0.63
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: rs7947951; hg19: chr11-13356030;