12-27344516-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-27344516-G-A is Benign according to our data. Variant chr12-27344516-G-A is described in ClinVar as [protective]. Clinvar id is 1693605.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.31+11413G>A		intron_variant		ENST00000266503.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.31+11413G>A		intron_variant		1	NM_020183.6	P2

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

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.231

Alfa AF: 0.211 Hom.: 7330

Bravo AF: 0.258

Asia WGS AF: 0.445 AC: 1545 AN: 3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Benign:1

protective, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.5
Dann	Benign	0.73

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: rs11048977; hg19: chr12-27497449; COSMIC: COSV99668228;