12-27402904-C-T

Variant names:

• chr12-27402904-C-T
• rs2306073
• NM_020183.6:c.1477+227C>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.1477+227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,976 control chromosomes in the GnomAD database, including 11,199 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 0.37 (11199 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 2 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]

BMAL2-AS1 (HGNC:49892): (BMAL2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 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.1477+227C>T		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.1510+227C>T		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.1468+227C>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.1477+227C>T		intron	N/A	ENSP00000266503.5	Q8WYA1-1
	BMAL2	ENST00000311001.9	TSL:1	c.1435+227C>T		intron	N/A	ENSP00000312247.5	Q8WYA1-2
	BMAL2	ENST00000395901.6	TSL:1	c.1366+227C>T		intron	N/A	ENSP00000379238.2	Q8WYA1-3

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56592 AN: 151858 Hom.: 11181 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.373 AC: 56660 AN: 151976 Hom.: 11199 Cov.: 32 AF XY: 0.376 AC XY: 27973 AN XY: 74304

African (AFR) AF: 0.475 AC: 19663 AN: 41436

American (AMR) AF: 0.289 AC: 4416 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3468

East Asian (EAS) AF: 0.587 AC: 3037 AN: 5172

South Asian (SAS) AF: 0.496 AC: 2393 AN: 4820

European-Finnish (FIN) AF: 0.362 AC: 3812 AN: 10544

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21632 AN: 67940

Other (OTH) AF: 0.334 AC: 706 AN: 2112

Alfa AF: 0.329 Hom.: 5167

Bravo AF: 0.368

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.43
DANN	Benign	0.69
PhyloP100		-1.4
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: rs2306073; hg19: chr12-27555837;