chr11-13302595-T-G

Variant names:

• chr11-13302595-T-G
• rs6486120
• NM_001297719.2:c.-262-7392T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-262-7392T>G		intron_variant	Intron 1 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-262-7392T>G		intron_variant	Intron 1 of 19	1	NM_001297719.2	ENSP00000384517.1

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

African (AFR) AF: 0.313 AC: 12992 AN: 41470

American (AMR) AF: 0.592 AC: 9047 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2358 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2575 AN: 5164

South Asian (SAS) AF: 0.669 AC: 3219 AN: 4814

European-Finnish (FIN) AF: 0.736 AC: 7781 AN: 10578

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47949 AN: 67984

Other (OTH) AF: 0.617 AC: 1304 AN: 2114

Alfa AF: 0.671 Hom.: 15931

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
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6486120; hg19: chr11-13324142;