rs1982350

Positions:

• chr11-13328584-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-135+2117A>G		intron_variant		ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-135+2117A>G		intron_variant		1	NM_001297719.2	ENSP00000384517	P4

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

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.611

Alfa AF: 0.614 Hom.: 35943

Bravo AF: 0.568

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs1982350; hg19: chr11-13350131;