rs4964060

chr12-27380434-A-Gchr12-27380434-A-T

Variant summary

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

The NM_020183.6(BMAL2):c.484+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,609,668 control chromosomes in the GnomAD database, including 262,463 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 (20646 hom., cov: 31)
  • Exomes 𝑓: 0.57 (241817 hom.)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

Genes affected

BMAL2 (HGNC:18984): (basic helix-loop-helix ARNT like 2) This gene encodes a basic helix-loop-helix transcription factor belonging to the PAS (PER, ARNT, SIM) superfamily. The PAS proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. This protein forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. Consistent with its role as a biologically relevant partner of circadian and hypoxia factors, this protein is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.484+30A>G		intron_variant		ENST00000266503.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.484+30A>G		intron_variant		1	NM_020183.6	P2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74491 AN: 151862 Hom.: 20633 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.541

GnomAD3 exomes AF: 0.562 AC: 140383 AN: 249836 Hom.: 41879 AF XY: 0.561 AC XY: 75681 AN XY: 134984

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.752

Gnomad ASJ exome AF: 0.703

Gnomad EAS exome AF: 0.337

Gnomad SAS exome AF: 0.472

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.569 AC: 829478 AN: 1457688 Hom.: 241817 Cov.: 32 AF XY: 0.568 AC XY: 411470 AN XY: 725022

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.704

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.490 AC: 74527 AN: 151980 Hom.: 20646 Cov.: 31 AF XY: 0.492 AC XY: 36569 AN XY: 74262

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.542

Alfa AF: 0.587 Hom.: 36310

Bravo AF: 0.487

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.74
Dann	Benign	0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs4964060; hg19: chr12-27533367; COSMIC: COSV53826263; COSMIC: COSV53826263;