11-13375362-C-T

Variant names:

• chr11-13375362-C-T
• rs11022780
• NM_001297719.2:c.1175-250C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):​c.1175-250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,028 control chromosomes in the GnomAD database, including 15,933 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 0.44 (15933 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.1175-250C>T		intron_variant	Intron 14 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.1175-250C>T		intron_variant	Intron 14 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66819 AN: 151908 Hom.: 15932 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.440 AC: 66844 AN: 152028 Hom.: 15933 Cov.: 33 AF XY: 0.443 AC XY: 32934 AN XY: 74320

African (AFR) AF: 0.273 AC: 11324 AN: 41464

American (AMR) AF: 0.403 AC: 6162 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1931 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5160

South Asian (SAS) AF: 0.621 AC: 2985 AN: 4810

European-Finnish (FIN) AF: 0.567 AC: 5989 AN: 10566

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35680 AN: 67970

Other (OTH) AF: 0.449 AC: 947 AN: 2108

Alfa AF: 0.504 Hom.: 31825

Bravo AF: 0.414

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.50
PhyloP100		-0.0020
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: rs11022780; hg19: chr11-13396909;