Variant rs284654 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000709.4(BCKDHA):c.995+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,609,446 control chromosomes in the GnomAD database, including 296,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30481 hom., cov: 31)

Exomes 𝑓: 0.60 ( 266512 hom. )

Consequence

BCKDHA
NM_000709.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.91

Variant links:

Genes affected

BCKDHA (HGNC:986): (branched chain keto acid dehydrogenase E1 subunit alpha) The branched-chain alpha-keto acid (BCAA) dehydrogenase (BCKD) complex is an innter mitochondrial enzyme complex that catalyzes the second major step in the catabolism of the branched-chain amino acids leucine, isoleucine, and valine. The BCKD complex consists of three catalytic components: a heterotetrameric (alpha2-beta2) branched-chain alpha-keto acid decarboxylase (E1), a dihydrolipoyl transacylase (E2), and a dihydrolipoamide dehydrogenase (E3). This gene encodes the alpha subunit of the decarboxylase (E1) component. Mutations in this gene result in maple syrup urine disease, type IA. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

BCKDHA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 19-41422819-G-A is Benign according to our data. Variant chr19-41422819-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 93387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCKDHA	NM_000709.4 linkuse as main transcript	c.995+49G>A		intron_variant		ENST00000269980.7	NP_000700.1
BCKDHA	NM_001164783.2 linkuse as main transcript	c.992+49G>A		intron_variant			NP_001158255.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
BCKDHA	ENST00000269980.7 linkuse as main transcript	c.995+49G>A	intron_variant	1	NM_000709.4	ENSP00000269980	P1	P12694-1
BCKDHA	ENST00000457836.6 linkuse as main transcript	c.929+49G>A	intron_variant	2		ENSP00000416000		P12694-2
BCKDHA	ENST00000542943.5 linkuse as main transcript	c.908+49G>A	intron_variant	5		ENSP00000440345

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95303

AN:

151664

Hom.:

30457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.724

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.617

GnomAD3 exomes

AF:

0.583

AC:

144063

AN:

247068

Hom.:

42722

AF XY:

0.584

AC XY:

78241

AN XY:

133878

show subpopulations

Gnomad AFR exome

AF:

0.725

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.428

Gnomad SAS exome

AF:

0.587

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.603

GnomAD4 exome

AF:

0.603

AC:

878385

AN:

1457664

Hom.:

266512

Cov.:

AF XY:

0.602

AC XY:

436531

AN XY:

725144

show subpopulations

Gnomad4 AFR exome

AF:

0.731

Gnomad4 AMR exome

AF:

0.478

Gnomad4 ASJ exome

AF:

0.622

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.582

Gnomad4 FIN exome

AF:

0.656

Gnomad4 NFE exome

AF:

0.607

Gnomad4 OTH exome

AF:

0.606

GnomAD4 genome

AF:

0.628

AC:

95373

AN:

151782

Hom.:

30481

Cov.:

AF XY:

0.627

AC XY:

46467

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.724

Gnomad4 AMR

AF:

0.549

Gnomad4 ASJ

AF:

0.623

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.585

Gnomad4 FIN

AF:

0.659

Gnomad4 NFE

AF:

0.600

Gnomad4 OTH

AF:

0.616

Alfa

AF:

0.576

Hom.:

5415

Bravo

AF:

0.624

Asia WGS

AF:

0.531

AC:

1845

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 12, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.073

DANN

Benign

0.53

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