rs4964060

Variant names:

• chr12-27380434-A-G
• rs4964060
• NM_020183.6:c.484+30A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-27380434-A-G
• chr12-27380434-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020183.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	NM_020183.6	MANE Select	c.484+30A>G		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.517+30A>G		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.475+30A>G		intron	N/A	NP_001381454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	ENST00000266503.10	TSL:1 MANE Select	c.484+30A>G		intron	N/A	ENSP00000266503.5
	BMAL2	ENST00000311001.9	TSL:1	c.442+30A>G		intron	N/A	ENSP00000312247.5
	BMAL2	ENST00000395901.6	TSL:1	c.373+30A>G		intron	N/A	ENSP00000379238.2

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

GnomAD2 exomes AF: 0.562 AC: 140383 AN: 249836 AF XY: 0.561

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 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

African (AFR) AF: 0.214 AC: 7133 AN: 33392

American (AMR) AF: 0.743 AC: 33143 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 18305 AN: 26008

East Asian (EAS) AF: 0.297 AC: 11779 AN: 39630

South Asian (SAS) AF: 0.474 AC: 40696 AN: 85876

European-Finnish (FIN) AF: 0.572 AC: 30526 AN: 53322

Middle Eastern (MID) AF: 0.589 AC: 3390 AN: 5752

European-Non Finnish (NFE) AF: 0.587 AC: 651344 AN: 1108908

Other (OTH) AF: 0.551 AC: 33162 AN: 60220

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

African (AFR) AF: 0.226 AC: 9376 AN: 41462

American (AMR) AF: 0.682 AC: 10428 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2416 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1648 AN: 5146

South Asian (SAS) AF: 0.462 AC: 2221 AN: 4806

European-Finnish (FIN) AF: 0.583 AC: 6159 AN: 10568

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40406 AN: 67932

Other (OTH) AF: 0.542 AC: 1143 AN: 2110

Alfa AF: 0.563 Hom.: 77070

Bravo AF: 0.487

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.74
DANN	Benign	0.21
PhyloP100		-0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4964060; hg19: chr12-27533367; COSMIC: COSV53826263; COSMIC: COSV53826263;