rs7304939

Variant names:

• chr12-27391412-C-T
• rs7304939
• NM_020183.6:c.919+1173C>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.919+1173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,212 control chromosomes in the GnomAD database, including 1,376 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 0.12 (1376 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• 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]

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL2	NM_020183.6	c.919+1173C>T		intron_variant	Intron 9 of 16	ENST00000266503.10	NP_064568.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10	c.919+1173C>T		intron_variant	Intron 9 of 16	1	NM_020183.6	ENSP00000266503.5
BMAL2	ENST00000457040.6	c.772+1173C>T		intron_variant	Intron 7 of 14	1		ENSP00000400185.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18067 AN: 152094 Hom.: 1363 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.0991

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

GnomAD4 genome AF: 0.119 AC: 18118 AN: 152212 Hom.: 1376 Cov.: 32 AF XY: 0.116 AC XY: 8665 AN XY: 74418

African (AFR) AF: 0.207 AC: 8576 AN: 41492

American (AMR) AF: 0.0659 AC: 1008 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 178 AN: 3466

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5188

South Asian (SAS) AF: 0.109 AC: 525 AN: 4824

European-Finnish (FIN) AF: 0.0905 AC: 961 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0955 AC: 6496 AN: 68016

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.0984 Hom.: 1385

Bravo AF: 0.119

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.20
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: rs7304939; hg19: chr12-27544345; COSMIC: COSV99668240;