Variant rs3217385 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000709.4(BCKDHA):c.996-33dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,596,250 control chromosomes in the GnomAD database, including 301,111 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33815 hom., cov: 0)

Exomes 𝑓: 0.61 ( 267296 hom. )

Consequence

BCKDHA
NM_000709.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.230

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-41422962-G-GC is Benign according to our data. Variant chr19-41422962-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 93389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCKDHA	NM_000709.4 linkuse as main transcript	c.996-33dup		intron_variant		ENST00000269980.7
BCKDHA	NM_001164783.2 linkuse as main transcript	c.993-33dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCKDHA	ENST00000269980.7 linkuse as main transcript	c.996-33dup		intron_variant		1	NM_000709.4	P1	P12694-1
BCKDHA	ENST00000457836.6 linkuse as main transcript	c.972dup	p.Thr325HisfsTer19	frameshift_variant	8/9	2			P12694-2
BCKDHA	ENST00000542943.5 linkuse as main transcript	c.909-33dup		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99667

AN:

151840

Hom.:

33773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.820

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.638

GnomAD3 exomes

AF:

0.590

AC:

129959

AN:

220434

Hom.:

39155

AF XY:

0.589

AC XY:

70189

AN XY:

119194

show subpopulations

Gnomad AFR exome

AF:

0.823

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.624

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.586

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.604

Gnomad OTH exome

AF:

0.607

GnomAD4 exome

AF:

0.606

AC:

874637

AN:

1444292

Hom.:

267296

Cov.:

AF XY:

0.604

AC XY:

433268

AN XY:

716882

show subpopulations

Gnomad4 AFR exome

AF:

0.832

Gnomad4 AMR exome

AF:

0.483

Gnomad4 ASJ exome

AF:

0.623

Gnomad4 EAS exome

AF:

0.458

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.654

Gnomad4 NFE exome

AF:

0.607

Gnomad4 OTH exome

AF:

0.613

GnomAD4 genome

AF:

0.657

AC:

99762

AN:

151958

Hom.:

33815

Cov.:

AF XY:

0.654

AC XY:

48545

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.821

Gnomad4 AMR

AF:

0.560

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.600

Gnomad4 OTH

AF:

0.638

Alfa

AF:

0.624

Hom.:

5474

Bravo

AF:

0.656

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

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)	Aug 23, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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