12-27336397-G-T

Position:

• chr12-27336397-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020183.6(BMAL2):​c.31+3294G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,978 control chromosomes in the GnomAD database, including 12,323 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 0.40 (12323 hom., cov: 31)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL2	NM_020183.6	c.31+3294G>T		intron_variant		ENST00000266503.10	NP_064568.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10	c.31+3294G>T		intron_variant		1	NM_020183.6	ENSP00000266503	P2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60772 AN: 151860 Hom.: 12323 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.400 AC: 60781 AN: 151978 Hom.: 12323 Cov.: 31 AF XY: 0.399 AC XY: 29607 AN XY: 74288

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.458

Alfa AF: 0.412 Hom.: 13050

Bravo AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.75

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: rs4964052; hg19: chr12-27489330;