rs3789327

Variant names:

• chr11-13363769-A-G
• rs3789327
• NM_001297719.2:c.460-1731A>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.460-1731A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,018 control chromosomes in the GnomAD database, including 21,701 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 0.53 (21701 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31
• Publications: 36 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.460-1731A>G		intron_variant	Intron 9 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.460-1731A>G		intron_variant	Intron 9 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79962 AN: 151902 Hom.: 21650 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.527 AC: 80082 AN: 152018 Hom.: 21701 Cov.: 31 AF XY: 0.528 AC XY: 39195 AN XY: 74300

African (AFR) AF: 0.642 AC: 26646 AN: 41474

American (AMR) AF: 0.589 AC: 8998 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1594 AN: 5160

South Asian (SAS) AF: 0.613 AC: 2948 AN: 4812

European-Finnish (FIN) AF: 0.443 AC: 4673 AN: 10548

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31916 AN: 67966

Other (OTH) AF: 0.530 AC: 1117 AN: 2108

Alfa AF: 0.495 Hom.: 32567

Bravo AF: 0.540

Asia WGS AF: 0.492 AC: 1710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0060
DANN	Benign	0.27
PhyloP100		-3.3
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: rs3789327; hg19: chr11-13385316;