rs7924734

chr11-13329200-A-Gchr11-13329200-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):c.-135+2733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,806 control chromosomes in the GnomAD database, including 5,103 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 0.25 (5103 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001297719.2	c.-135+2733A>G		intron_variant		ENST00000403290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL1	ENST00000403290.6	c.-135+2733A>G		intron_variant		1	NM_001297719.2	P4

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38436 AN: 151688 Hom.: 5102 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.253 AC: 38450 AN: 151806 Hom.: 5103 Cov.: 32 AF XY: 0.258 AC XY: 19144 AN XY: 74158

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.239

Alfa AF: 0.252 Hom.: 10143

Bravo AF: 0.245

Asia WGS AF: 0.340 AC: 1184 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	0.66
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7924734; hg19: chr11-13350747;