Variant 12-27380434-A-G 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.484+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,609,668 control chromosomes in the GnomAD database, including 262,463 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 0.49 ( 20646 hom., cov: 31)

Exomes 𝑓: 0.57 ( 241817 hom. )

Consequence

BMAL2
NM_020183.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.907

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:

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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=-0.94).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 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.484+30A>G		intron_variant		ENST00000266503.10	NP_064568.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10 linkuse as main transcript	c.484+30A>G		intron_variant		1	NM_020183.6	ENSP00000266503	P2	Q8WYA1-1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74491

AN:

151862

Hom.:

20633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.541

GnomAD3 exomes

AF:

0.562

AC:

140383

AN:

249836

Hom.:

41879

AF XY:

0.561

AC XY:

75681

AN XY:

134984

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.752

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.337

Gnomad SAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.569

AC:

829478

AN:

1457688

Hom.:

241817

Cov.:

AF XY:

0.568

AC XY:

411470

AN XY:

725022

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.743

Gnomad4 ASJ exome

AF:

0.704

Gnomad4 EAS exome

AF:

0.297

Gnomad4 SAS exome

AF:

0.474

Gnomad4 FIN exome

AF:

0.572

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.551

GnomAD4 genome

AF:

0.490

AC:

74527

AN:

151980

Hom.:

20646

Cov.:

AF XY:

0.492

AC XY:

36569

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.682

Gnomad4 ASJ

AF:

0.696

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.462

Gnomad4 FIN

AF:

0.583

Gnomad4 NFE

AF:

0.595

Gnomad4 OTH

AF:

0.542

Alfa

AF:

0.587

Hom.:

36310

Bravo

AF:

0.487

Asia WGS

AF:

0.370

AC:

1288

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.74

DANN

Benign

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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