12-27348173-G-A

Variant names:

• chr12-27348173-G-A
• rs7958822
• NM_020183.6:c.31+15070G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020183.6(BMAL2):​c.31+15070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,026 control chromosomes in the GnomAD database, including 14,287 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 0.43 (14287 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 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.31+15070G>A		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.64+15037G>A		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.64+15037G>A		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.31+15070G>A		intron	N/A	ENSP00000266503.5
	BMAL2	ENST00000311001.9	TSL:1	c.31+15070G>A		intron	N/A	ENSP00000312247.5
	BMAL2	ENST00000395901.6	TSL:1	c.64+15037G>A		intron	N/A	ENSP00000379238.2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65348 AN: 151908 Hom.: 14278 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.430 AC: 65401 AN: 152026 Hom.: 14287 Cov.: 32 AF XY: 0.431 AC XY: 32001 AN XY: 74288

African (AFR) AF: 0.397 AC: 16464 AN: 41456

American (AMR) AF: 0.512 AC: 7824 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3466

East Asian (EAS) AF: 0.252 AC: 1307 AN: 5182

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4818

European-Finnish (FIN) AF: 0.458 AC: 4826 AN: 10536

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30185 AN: 67986

Other (OTH) AF: 0.470 AC: 988 AN: 2100

Alfa AF: 0.431 Hom.: 4188

Bravo AF: 0.438

Asia WGS AF: 0.339 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.52
PhyloP100		-0.67
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: rs7958822; hg19: chr12-27501106;