12-27344516-G-A

Variant names:

• chr12-27344516-G-A
• rs11048977
• NM_020183.6:c.31+11413G>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+11413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,130 control chromosomes in the GnomAD database, including 5,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency: Genomes: 𝑓 0.26 (5788 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: 0.305
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	NM_020183.6	MANE Select	c.31+11413G>A		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.64+11380G>A		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.64+11380G>A		intron	N/A	NP_001381454.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	ENST00000266503.10	TSL:1 MANE Select	c.31+11413G>A		intron	N/A	ENSP00000266503.5	Q8WYA1-1
	BMAL2	ENST00000311001.9	TSL:1	c.31+11413G>A		intron	N/A	ENSP00000312247.5	Q8WYA1-2
	BMAL2	ENST00000395901.6	TSL:1	c.64+11380G>A		intron	N/A	ENSP00000379238.2	Q8WYA1-3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39240 AN: 152012 Hom.: 5794 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.258 AC: 39264 AN: 152130 Hom.: 5788 Cov.: 32 AF XY: 0.265 AC XY: 19702 AN XY: 74382

African (AFR) AF: 0.309 AC: 12800 AN: 41476

American (AMR) AF: 0.258 AC: 3942 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3536 AN: 5174

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4820

European-Finnish (FIN) AF: 0.245 AC: 2594 AN: 10586

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13488 AN: 67992

Other (OTH) AF: 0.231 AC: 488 AN: 2116

Alfa AF: 0.219 Hom.: 17308

Bravo AF: 0.258

Asia WGS AF: 0.445 AC: 1545 AN: 3478

ClinVar

ClinVar submissions

Significance: protective

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		0.30
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: rs11048977; hg19: chr12-27497449; COSMIC: COSV99668228;