chr12-27369990-G-A

Variant names:

• chr12-27369990-G-A
• rs17413842
• NM_020183.6:c.183-139G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	NM_020183.6	MANE Select	c.183-139G>A		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.216-139G>A		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.216-139G>A		intron	N/A	NP_001381454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	ENST00000266503.10	TSL:1 MANE Select	c.183-139G>A		intron	N/A	ENSP00000266503.5
	BMAL2	ENST00000311001.9	TSL:1	c.183-139G>A		intron	N/A	ENSP00000312247.5
	BMAL2	ENST00000395901.6	TSL:1	c.215+1578G>A		intron	N/A	ENSP00000379238.2

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

African (AFR) AF: 0.0642 AC: 888 AN: 13828

American (AMR) AF: 0.0879 AC: 2193 AN: 24944

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1377 AN: 13640

East Asian (EAS) AF: 0.0579 AC: 1927 AN: 33300

South Asian (SAS) AF: 0.127 AC: 5895 AN: 46504

European-Finnish (FIN) AF: 0.162 AC: 6133 AN: 37868

Middle Eastern (MID) AF: 0.0802 AC: 164 AN: 2044

European-Non Finnish (NFE) AF: 0.165 AC: 46593 AN: 283056

Other (OTH) AF: 0.134 AC: 3581 AN: 26700

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

African (AFR) AF: 0.0633 AC: 2628 AN: 41508

American (AMR) AF: 0.0999 AC: 1526 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3466

East Asian (EAS) AF: 0.0625 AC: 324 AN: 5186

South Asian (SAS) AF: 0.127 AC: 613 AN: 4816

European-Finnish (FIN) AF: 0.169 AC: 1784 AN: 10576

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11564 AN: 67948

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.141 Hom.: 293

Bravo AF: 0.116

Asia WGS AF: 0.113 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

dbSNP: rs17413842; hg19: chr12-27522923;