NM_001297719.2:c.-134-4770C>G

Variant names:

• chr11-13345175-C-G
• rs12421530
• NM_001297719.2:c.-134-4770C>G

Variant summary

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

The NM_001297719.2(BMAL1):​c.-134-4770C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,110 control chromosomes in the GnomAD database, including 19,636 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 0.49 (19636 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-134-4770C>G		intron_variant	Intron 3 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-134-4770C>G		intron_variant	Intron 3 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74526 AN: 151992 Hom.: 19639 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.490 AC: 74536 AN: 152110 Hom.: 19636 Cov.: 33 AF XY: 0.480 AC XY: 35656 AN XY: 74360

African (AFR) AF: 0.367 AC: 15214 AN: 41464

American (AMR) AF: 0.438 AC: 6701 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2004 AN: 3472

East Asian (EAS) AF: 0.140 AC: 726 AN: 5176

South Asian (SAS) AF: 0.400 AC: 1930 AN: 4824

European-Finnish (FIN) AF: 0.476 AC: 5037 AN: 10582

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41214 AN: 67982

Other (OTH) AF: 0.540 AC: 1142 AN: 2114

Alfa AF: 0.536 Hom.: 2802

Bravo AF: 0.482

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.47
PhyloP100		-0.71
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: rs12421530; hg19: chr11-13366722;