rs7126303

Positions:

• chr11-13348988-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.-134-957C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,982 control chromosomes in the GnomAD database, including 19,136 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 0.48 (19136 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-134-957C>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.-134-957C>T		intron_variant		1	NM_001297719.2	ENSP00000384517	P4

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73599 AN: 151862 Hom.: 19138 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.484 AC: 73611 AN: 151982 Hom.: 19136 Cov.: 32 AF XY: 0.474 AC XY: 35200 AN XY: 74294

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.540

Alfa AF: 0.553 Hom.: 16316

Bravo AF: 0.477

Asia WGS AF: 0.300 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.65

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: rs7126303; hg19: chr11-13370535;