12-27414903-C-G

Variant names:

• chr12-27414903-C-G
• rs11049004
• NM_020183.6:c.1587-966C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020183.6(BMAL2):​c.1587-966C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 151,880 control chromosomes in the GnomAD database, including 629 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 0.089 (629 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020183.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	NM_020183.6	MANE Select	c.1587-966C>G		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.1620-966C>G		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.1578-966C>G		intron	N/A	NP_001381454.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	ENST00000266503.10	TSL:1 MANE Select	c.1587-966C>G		intron	N/A	ENSP00000266503.5	Q8WYA1-1
	BMAL2	ENST00000311001.9	TSL:1	c.1545-966C>G		intron	N/A	ENSP00000312247.5	Q8WYA1-2
	BMAL2	ENST00000395901.6	TSL:1	c.1476-966C>G		intron	N/A	ENSP00000379238.2	Q8WYA1-3

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13541 AN: 151762 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0821

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

GnomAD4 genome AF: 0.0895 AC: 13588 AN: 151880 Hom.: 629 Cov.: 32 AF XY: 0.0905 AC XY: 6720 AN XY: 74228

African (AFR) AF: 0.112 AC: 4644 AN: 41414

American (AMR) AF: 0.0610 AC: 931 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3472

East Asian (EAS) AF: 0.117 AC: 607 AN: 5178

South Asian (SAS) AF: 0.128 AC: 617 AN: 4810

European-Finnish (FIN) AF: 0.0909 AC: 956 AN: 10522

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0789 AC: 5356 AN: 67906

Other (OTH) AF: 0.0821 AC: 173 AN: 2106

Alfa AF: 0.0763 Hom.: 58

Bravo AF: 0.0858

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.83
PhyloP100		-0.41
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11049004;

hg19: chr12-27567836;