12-27336397-G-T

Variant names:

• chr12-27336397-G-T
• rs4964052
• NM_020183.6:c.31+3294G>T

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+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
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 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+3294G>T		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.64+3261G>T		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.64+3261G>T		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+3294G>T		intron	N/A	ENSP00000266503.5	Q8WYA1-1
	BMAL2	ENST00000311001.9	TSL:1	c.31+3294G>T		intron	N/A	ENSP00000312247.5	Q8WYA1-2
	BMAL2	ENST00000395901.6	TSL:1	c.64+3261G>T		intron	N/A	ENSP00000379238.2	Q8WYA1-3

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

African (AFR) AF: 0.377 AC: 15604 AN: 41444

American (AMR) AF: 0.344 AC: 5247 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2213 AN: 5158

South Asian (SAS) AF: 0.346 AC: 1667 AN: 4814

European-Finnish (FIN) AF: 0.423 AC: 4472 AN: 10566

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.420 AC: 28509 AN: 67946

Other (OTH) AF: 0.458 AC: 969 AN: 2116

Alfa AF: 0.411 Hom.: 34072

Bravo AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.75
PhyloP100		0.025
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: rs4964052; hg19: chr12-27489330;