12-27363909-T-G

Variant names:

• chr12-27363909-T-G
• rs4964057
• NM_020183.6:c.32-4353T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020183.6(BMAL2):​c.32-4353T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,042 control chromosomes in the GnomAD database, including 7,222 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 0.29 (7222 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL2	NM_020183.6	c.32-4353T>G		intron_variant	Intron 1 of 16	ENST00000266503.10	NP_064568.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10	c.32-4353T>G		intron_variant	Intron 1 of 16	1	NM_020183.6	ENSP00000266503.5

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44136 AN: 151924 Hom.: 7218 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.290 AC: 44156 AN: 152042 Hom.: 7222 Cov.: 32 AF XY: 0.292 AC XY: 21705 AN XY: 74306

African (AFR) AF: 0.154 AC: 6400 AN: 41522

American (AMR) AF: 0.210 AC: 3202 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2300 AN: 5174

South Asian (SAS) AF: 0.308 AC: 1481 AN: 4816

European-Finnish (FIN) AF: 0.414 AC: 4365 AN: 10544

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24667 AN: 67926

Other (OTH) AF: 0.283 AC: 597 AN: 2106

Alfa AF: 0.338 Hom.: 1866

Bravo AF: 0.268

Asia WGS AF: 0.379 AC: 1319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-1.2
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: rs4964057; hg19: chr12-27516842;