12-27352018-C-T

Variant names:

• chr12-27352018-C-T
• rs922270
• NM_020183.6:c.32-16244C>T

Variant summary

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

The NM_001394524.1(BMAL2):​c.65-16244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,218 control chromosomes in the GnomAD database, including 59,207 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 0.88 (59207 hom., cov: 32)
• Consequence: BMAL2 NM_001394524.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 6 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394524.1. 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.32-16244C>T		intron	N/A	NP_064568.3
	BMAL2	NM_001394524.1		c.65-16244C>T		intron	N/A	NP_001381453.1
	BMAL2	NM_001394525.1		c.65-16244C>T		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.32-16244C>T		intron	N/A	ENSP00000266503.5
	BMAL2	ENST00000311001.9	TSL:1	c.32-16244C>T		intron	N/A	ENSP00000312247.5
	BMAL2	ENST00000395901.6	TSL:1	c.65-16244C>T		intron	N/A	ENSP00000379238.2

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134084 AN: 152100 Hom.: 59172 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.881 AC: 134176 AN: 152218 Hom.: 59207 Cov.: 32 AF XY: 0.884 AC XY: 65746 AN XY: 74400

African (AFR) AF: 0.909 AC: 37780 AN: 41550

American (AMR) AF: 0.912 AC: 13933 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2804 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5180 AN: 5188

South Asian (SAS) AF: 0.819 AC: 3946 AN: 4816

European-Finnish (FIN) AF: 0.903 AC: 9563 AN: 10596

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58115 AN: 67996

Other (OTH) AF: 0.886 AC: 1872 AN: 2112

Alfa AF: 0.863 Hom.: 38016

Bravo AF: 0.886

Asia WGS AF: 0.919 AC: 3196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.24
PhyloP100		-0.51
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: rs922270; hg19: chr12-27504951;