rs2290034

Positions:

• chr11-13385637-C-T

Variant summary

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

The NM_001297719.2(BMAL1):​c.1618-52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,362,966 control chromosomes in the GnomAD database, including 23,457 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 0.19 (2863 hom., cov: 32)
  • Exomes 𝑓: 0.18 (20594 hom.)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.1618-52C>T		intron_variant		ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.1618-52C>T		intron_variant		1	NM_001297719.2	ENSP00000384517	P4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29168 AN: 152018 Hom.: 2854 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.179 AC: 216950 AN: 1210830 Hom.: 20594 Cov.: 16 AF XY: 0.176 AC XY: 107762 AN XY: 610892

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.192 AC: 29212 AN: 152136 Hom.: 2863 Cov.: 32 AF XY: 0.193 AC XY: 14324 AN XY: 74382

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.182

Alfa AF: 0.172 Hom.: 988

Bravo AF: 0.198

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.40

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: rs2290034; hg19: chr11-13407184;