Variant 12-27344516-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_020183.6(BMAL2):c.31+11413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,130 control chromosomes in the GnomAD database, including 5,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5788 hom., cov: 32)

Consequence

BMAL2
NM_020183.6 intron

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 0.305

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-27344516-G-A is Benign according to our data. Variant chr12-27344516-G-A is described in ClinVar as [protective]. Clinvar id is 1693605.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL2	NM_020183.6 linkuse as main transcript	c.31+11413G>A		intron_variant		ENST00000266503.10	NP_064568.3	Q8WYA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10 linkuse as main transcript	c.31+11413G>A		intron_variant		1	NM_020183.6	ENSP00000266503.5		Q8WYA1-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39240

AN:

152012

Hom.:

5794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.228

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

GnomAD4 genome

AF:

0.258

AC:

39264

AN:

152130

Hom.:

5788

Cov.:

AF XY:

0.265

AC XY:

19702

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.683

Gnomad4 SAS

AF:

0.341

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.211

Hom.:

7330

Bravo

AF:

0.258

Asia WGS

AF:

0.445

AC:

1545

AN:

3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to

Benign:1

protective, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.5

DANN

Benign

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over