11-13302595-T-G

Position:

• chr11-13302595-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001297719.2(BMAL1):​c.-262-7392T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,084 control chromosomes in the GnomAD database, including 27,713 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 0.58 (27713 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001297719.2	c.-262-7392T>G		intron_variant		ENST00000403290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL1	ENST00000403290.6	c.-262-7392T>G		intron_variant		1	NM_001297719.2	P4

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87882 AN: 151966 Hom.: 27697 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.578 AC: 87921 AN: 152084 Hom.: 27713 Cov.: 32 AF XY: 0.581 AC XY: 43214 AN XY: 74336

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.617

Alfa AF: 0.652 Hom.: 8627

Bravo AF: 0.560

Asia WGS AF: 0.592 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.82

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: rs6486120; hg19: chr11-13324142;