NM_001297719.2:c.-262-12947C>T

Variant names:

• chr11-13297040-C-T
• rs10766075
• NM_001297719.2:c.-262-12947C>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.-262-12947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,156 control chromosomes in the GnomAD database, including 5,989 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 0.27 (5989 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-262-12947C>T		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.-262-12947C>T		intron_variant	Intron 1 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41823 AN: 152038 Hom.: 5992 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.275 AC: 41841 AN: 152156 Hom.: 5989 Cov.: 33 AF XY: 0.277 AC XY: 20593 AN XY: 74376

African (AFR) AF: 0.222 AC: 9226 AN: 41510

American (AMR) AF: 0.344 AC: 5263 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3472

East Asian (EAS) AF: 0.504 AC: 2605 AN: 5168

South Asian (SAS) AF: 0.301 AC: 1454 AN: 4824

European-Finnish (FIN) AF: 0.251 AC: 2654 AN: 10588

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18643 AN: 67994

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.282 Hom.: 762

Bravo AF: 0.276

Asia WGS AF: 0.369 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.60
PhyloP100		0.30
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: rs10766075; hg19: chr11-13318587;