rs2290035

Variant names:

• chr11-13386224-T-A
• rs2290035
• NM_001297719.2:c.1721-372T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-13386224-T-A
• chr11-13386224-T-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.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
• Publications: 28 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=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 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.1721-372T>A		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.1736-372T>A		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.1736-372T>A		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.1721-372T>A		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.1718-372T>A		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000403482.7	TSL:1	c.1715-372T>A		intron	N/A	ENSP00000385897.3	O00327-7

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

African (AFR) AF: 0.331 AC: 13739 AN: 41472

American (AMR) AF: 0.413 AC: 6306 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1329 AN: 5170

South Asian (SAS) AF: 0.623 AC: 3006 AN: 4822

European-Finnish (FIN) AF: 0.585 AC: 6178 AN: 10568

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36608 AN: 67968

Other (OTH) AF: 0.467 AC: 983 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		0.41
Mutation Taster		=99/1	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: rs2290035; hg19: chr11-13407771;