chr12-27396250-T-C

Position:

• chr12-27396250-T-C

Variant summary

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

The NM_020183.6(BMAL2):​c.920-4284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,076 control chromosomes in the GnomAD database, including 3,059 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 0.17 (3059 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL2	NM_020183.6	c.920-4284T>C		intron_variant		ENST00000266503.10	NP_064568.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10	c.920-4284T>C		intron_variant		1	NM_020183.6	ENSP00000266503.5
BMAL2	ENST00000457040.6	c.773-4284T>C		intron_variant		1		ENSP00000400185.2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26289 AN: 151958 Hom.: 3036 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.173 AC: 26352 AN: 152076 Hom.: 3059 Cov.: 32 AF XY: 0.173 AC XY: 12889 AN XY: 74344

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.134

Alfa AF: 0.148 Hom.: 259

Bravo AF: 0.173

Asia WGS AF: 0.139 AC: 480 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.53

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: rs12299407; hg19: chr12-27549183;