rs10766077

chr11-13328234-G-Achr11-13328234-G-Cchr11-13328234-G-T

Variant summary

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

The NM_001297719.2(BMAL1):c.-135+1767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,908 control chromosomes in the GnomAD database, including 11,805 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 0.39 (11805 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001297719.2	c.-135+1767G>A		intron_variant		ENST00000403290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL1	ENST00000403290.6	c.-135+1767G>A		intron_variant		1	NM_001297719.2	P4

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59045 AN: 151790 Hom.: 11803 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.389 AC: 59075 AN: 151908 Hom.: 11805 Cov.: 32 AF XY: 0.396 AC XY: 29432 AN XY: 74250

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.357

Alfa AF: 0.377 Hom.: 14554

Bravo AF: 0.379

Asia WGS AF: 0.542 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.8
Dann	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10766077; hg19: chr11-13349781;