11-13328584-A-G

Variant names:

• chr11-13328584-A-G
• rs1982350
• NM_001297719.2:c.-135+2117A>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+2117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,938 control chromosomes in the GnomAD database, including 24,456 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 0.56 (24456 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839
• Publications: 23 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	NM_001297719.2	MANE Select	c.-135+2117A>G		intron	N/A	NP_001284648.1
	BMAL1	NM_001351807.2		c.-135+18525A>G		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-135+2117A>G		intron	N/A	NP_001338743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	ENST00000403290.6	TSL:1 MANE Select	c.-135+2117A>G		intron	N/A	ENSP00000384517.1
	BMAL1	ENST00000389707.8	TSL:1	c.-135+2117A>G		intron	N/A	ENSP00000374357.4
	BMAL1	ENST00000401424.6	TSL:1	c.-335+18525A>G		intron	N/A	ENSP00000385915.2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85691 AN: 151820 Hom.: 24444 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.564 AC: 85743 AN: 151938 Hom.: 24456 Cov.: 31 AF XY: 0.559 AC XY: 41507 AN XY: 74256

African (AFR) AF: 0.512 AC: 21191 AN: 41416

American (AMR) AF: 0.570 AC: 8685 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2074 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1835 AN: 5150

South Asian (SAS) AF: 0.487 AC: 2349 AN: 4826

European-Finnish (FIN) AF: 0.539 AC: 5694 AN: 10558

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42074 AN: 67960

Other (OTH) AF: 0.611 AC: 1287 AN: 2108

Alfa AF: 0.607 Hom.: 93270

Bravo AF: 0.568

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.37
PhyloP100		-0.84
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: rs1982350; hg19: chr11-13350131;