rs7958822

Positions:

• chr12-27348173-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.31+15070G>A		intron_variant		ENST00000266503.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.31+15070G>A		intron_variant		1	NM_020183.6	P2

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

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.470

Alfa AF: 0.438 Hom.: 1841

Bravo AF: 0.438

Asia WGS AF: 0.339 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.52

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: rs7958822; hg19: chr12-27501106;