rs4757142

chr11-13304148-G-A

Variant summary

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

The NM_001297719.2(BMAL1):c.-262-5839G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,848 control chromosomes in the GnomAD database, including 18,796 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 0.48 (18796 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001297719.2	c.-262-5839G>A		intron_variant		ENST00000403290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL1	ENST00000403290.6	c.-262-5839G>A		intron_variant		1	NM_001297719.2	P4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72122 AN: 151730 Hom.: 18792 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.475 AC: 72148 AN: 151848 Hom.: 18796 Cov.: 31 AF XY: 0.474 AC XY: 35190 AN XY: 74176

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.504

Alfa AF: 0.548 Hom.: 9428

Bravo AF: 0.461

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.63
Dann	Benign	0.66

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: rs4757142; hg19: chr11-13325695;