NM_001297719.2:c.-189-2949G>A

Variant names:

• chr11-13323464-G-A
• rs895683
• NM_001297719.2:c.-189-2949G>A

Variant summary

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

The NM_001297719.2(BMAL1):​c.-189-2949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,094 control chromosomes in the GnomAD database, including 50,155 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 0.81 (50155 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-189-2949G>A		intron_variant	Intron 2 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-189-2949G>A		intron_variant	Intron 2 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123129 AN: 151976 Hom.: 50144 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.810 AC: 123189 AN: 152094 Hom.: 50155 Cov.: 31 AF XY: 0.807 AC XY: 60005 AN XY: 74332

African (AFR) AF: 0.723 AC: 29964 AN: 41452

American (AMR) AF: 0.833 AC: 12754 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2881 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4146 AN: 5172

South Asian (SAS) AF: 0.781 AC: 3765 AN: 4818

European-Finnish (FIN) AF: 0.816 AC: 8614 AN: 10550

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58318 AN: 68008

Other (OTH) AF: 0.827 AC: 1749 AN: 2114

Alfa AF: 0.831 Hom.: 6042

Bravo AF: 0.807

Asia WGS AF: 0.784 AC: 2725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		0.044
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: rs895683; hg19: chr11-13345011;