rs11048980

Variant names:

• chr12-27350614-T-C
• rs11048980
• NM_020183.6:c.31+17511T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.8).
• 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 rank	MANE	Protein	UniProt
BMAL2	NM_020183.6	c.31+17511T>C		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.31+17511T>C		intron_variant	Intron 1 of 16	1	NM_020183.6	ENSP00000266503.5

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

African (AFR) AF: 0.0162 AC: 673 AN: 41570

American (AMR) AF: 0.0438 AC: 671 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 264 AN: 3472

East Asian (EAS) AF: 0.0399 AC: 207 AN: 5194

South Asian (SAS) AF: 0.0271 AC: 131 AN: 4832

European-Finnish (FIN) AF: 0.108 AC: 1149 AN: 10606

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7019 AN: 68004

Other (OTH) AF: 0.0520 AC: 110 AN: 2116

Alfa AF: 0.0904 Hom.: 969

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