11-13369925-C-A

Position:

• chr11-13369925-C-A

Variant summary

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

The ENST00000403290.6(BMAL1):​c.820+158C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,150 control chromosomes in the GnomAD database, including 924 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 0.097 (924 hom., cov: 32)
• Consequence: BMAL1 ENST00000403290.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.820+158C>A		intron_variant		ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.820+158C>A		intron_variant		1	NM_001297719.2	ENSP00000384517	P4

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14693 AN: 152032 Hom.: 924 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0952

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

GnomAD4 genome AF: 0.0968 AC: 14728 AN: 152150 Hom.: 924 Cov.: 32 AF XY: 0.0994 AC XY: 7391 AN XY: 74386

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.0850

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0966

Alfa AF: 0.0943 Hom.: 468

Bravo AF: 0.0993

Asia WGS AF: 0.123 AC: 425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.41

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: rs3816358; hg19: chr11-13391472;