chr12-27369990-G-A

Position:

• chr12-27369990-G-A

Variant summary

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

The NM_020183.6(BMAL2):​c.183-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 633,974 control chromosomes in the GnomAD database, including 6,792 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 0.13 (1390 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5402 hom.)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.183-139G>A		intron_variant		ENST00000266503.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.183-139G>A		intron_variant		1	NM_020183.6	P2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19136 AN: 151972 Hom.: 1388 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.143 AC: 68751 AN: 481884 Hom.: 5402 AF XY: 0.143 AC XY: 36700 AN XY: 256862

Gnomad4 AFR exome AF: 0.0642

Gnomad4 AMR exome AF: 0.0879

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0579

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.126 AC: 19146 AN: 152090 Hom.: 1390 Cov.: 32 AF XY: 0.125 AC XY: 9260 AN XY: 74340

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.0999

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.129

Alfa AF: 0.143 Hom.: 291

Bravo AF: 0.116

Asia WGS AF: 0.113 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.95
DANN	Benign	0.64

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: rs17413842; hg19: chr12-27522923;