12-27420700-C-T

Variant names:

• chr12-27420700-C-T
• rs2289709
• NM_020183.6:c.*168C>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.*168C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 777,024 control chromosomes in the GnomAD database, including 6,726 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 (1493 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5233 hom.)
• Consequence: BMAL2 NM_020183.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 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.*168C>T		3_prime_UTR	Exon 17 of 17	NP_064568.3
	BMAL2	NM_001394524.1		c.*168C>T		3_prime_UTR	Exon 17 of 17	NP_001381453.1
	BMAL2	NM_001394525.1		c.*168C>T		3_prime_UTR	Exon 16 of 16	NP_001381454.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL2	ENST00000266503.10	TSL:1 MANE Select	c.*168C>T		3_prime_UTR	Exon 17 of 17	ENSP00000266503.5	Q8WYA1-1
	BMAL2	ENST00000457040.6	TSL:1	c.*168C>T		3_prime_UTR	Exon 15 of 15	ENSP00000400185.2	H0Y5R1
	BMAL2-AS1	ENST00000500498.2	TSL:1	n.129+25797G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20395 AN: 152062 Hom.: 1472 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.127 AC: 79180 AN: 624844 Hom.: 5233 Cov.: 9 AF XY: 0.127 AC XY: 39410 AN XY: 309152

African (AFR) AF: 0.183 AC: 2450 AN: 13368

American (AMR) AF: 0.0676 AC: 761 AN: 11262

Ashkenazi Jewish (ASJ) AF: 0.0763 AC: 958 AN: 12548

East Asian (EAS) AF: 0.141 AC: 3575 AN: 25292

South Asian (SAS) AF: 0.166 AC: 3708 AN: 22394

European-Finnish (FIN) AF: 0.111 AC: 2990 AN: 26926

Middle Eastern (MID) AF: 0.144 AC: 316 AN: 2192

European-Non Finnish (NFE) AF: 0.126 AC: 60613 AN: 480926

Other (OTH) AF: 0.127 AC: 3809 AN: 29936

GnomAD4 genome AF: 0.134 AC: 20452 AN: 152180 Hom.: 1493 Cov.: 32 AF XY: 0.133 AC XY: 9895 AN XY: 74400

African (AFR) AF: 0.179 AC: 7435 AN: 41494

American (AMR) AF: 0.0884 AC: 1352 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3472

East Asian (EAS) AF: 0.120 AC: 624 AN: 5188

South Asian (SAS) AF: 0.163 AC: 785 AN: 4826

European-Finnish (FIN) AF: 0.103 AC: 1086 AN: 10592

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8473 AN: 67996

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.118 Hom.: 1890

Bravo AF: 0.132

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.74
PhyloP100		0.073
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: rs2289709; hg19: chr12-27573633; COSMIC: COSV99668248; COSMIC: COSV99668248;