Variant 12-27420700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Variant links:

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 links:

BMAL2-AS1 (HGNC:49892): (BMAL2 antisense RNA 1)

BMAL2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6 linkuse as main transcript	c.*168C>T		3_prime_UTR_variant	17/17	ENST00000266503.10
BMAL2-AS1	NR_109975.1 linkuse as main transcript	n.138+25797G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10 linkuse as main transcript	c.*168C>T	3_prime_UTR_variant	17/17	1	NM_020183.6	P2	Q8WYA1-1
BMAL2	ENST00000457040.6 linkuse as main transcript	c.*168C>T	3_prime_UTR_variant	15/15	1
BMAL2-AS1	ENST00000500498.2 linkuse as main transcript	n.129+25797G>A	intron_variant, non_coding_transcript_variant		1
BMAL2	ENST00000544915.5 linkuse as main transcript	c.*168C>T	3_prime_UTR_variant	16/16	5		A2	Q8WYA1-5

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20395

AN:

152062

Hom.:

1472

Cov.:

show subpopulations

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.:

AF XY:

0.127

AC XY:

39410

AN XY:

309152

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.0676

Gnomad4 ASJ exome

AF:

0.0763

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.134

AC:

20452

AN:

152180

Hom.:

1493

Cov.:

AF XY:

0.133

AC XY:

9895

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.0884

Gnomad4 ASJ

AF:

0.0804

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.116

Hom.:

1422

Bravo

AF:

0.132

Asia WGS

AF:

0.152

AC:

529

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

DANN

Benign

0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over