rs11048980

Positions:

• chr12-27350614-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.31+17511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 152,308 control chromosomes in the GnomAD database, including 472 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 0.068 (472 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.31+17511T>C		intron_variant		ENST00000266503.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.31+17511T>C		intron_variant		1	NM_020183.6	P2

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10381 AN: 152190 Hom.: 472 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0760

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0525

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

GnomAD4 genome AF: 0.0681 AC: 10377 AN: 152308 Hom.: 472 Cov.: 32 AF XY: 0.0671 AC XY: 5000 AN XY: 74476

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0760

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.0271

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0937 Hom.: 833

Bravo AF: 0.0600

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.88

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: rs11048980; hg19: chr12-27503547; COSMIC: COSV99668232;