rs2290035

Positions:

• chr11-13386224-T-A
• chr11-13386224-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):​c.1721-372T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,042 control chromosomes in the GnomAD database, including 17,339 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 0.46 (17339 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001297719.2	c.1721-372T>A		intron_variant		ENST00000403290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL1	ENST00000403290.6	c.1721-372T>A		intron_variant		1	NM_001297719.2	P4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70590 AN: 151924 Hom.: 17335 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.464 AC: 70622 AN: 152042 Hom.: 17339 Cov.: 32 AF XY: 0.467 AC XY: 34743 AN XY: 74328

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.467

Alfa AF: 0.502 Hom.: 2441

Bravo AF: 0.440

Asia WGS AF: 0.436 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.89

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: rs2290035; hg19: chr11-13407771;