dbSNP rs56314408: BCKDK:c.-662T>C (chr16-31106068-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000394951.5(BCKDK):c.-662T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,002 control chromosomes in the GnomAD database, including 26,840 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 0.58 ( 26826 hom., cov: 32)

Exomes 𝑓: 0.68 ( 14 hom. )

Consequence

BCKDK
ENST00000394951.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

Publications

21 publications found

Variant links:

Genes affected

BCKDK (HGNC:16902): (branched chain keto acid dehydrogenase kinase) The branched-chain alpha-ketoacid dehydrogenase complex (BCKD) is an important regulator of the valine, leucine, and isoleucine catabolic pathways. The protein encoded by this gene is found in the mitochondrion, where it phosphorylates and inactivates BCKD. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

BCKDK Gene-Disease associations (from GenCC):

branched-chain keto acid dehydrogenase kinase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

BCKDK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCKDK	ENST00000394951.5 link	c.-662T>C		upstream_gene_variant		5		ENSP00000378405.1		O14874-1

Frequencies

GnomAD3 genomes

AF:

0.584

AC:

88688

AN:

151824

Hom.:

26792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.546

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.817

Gnomad FIN

AF:

0.611

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.545

GnomAD4 exome

AF:

0.683

AC:

AN:

Hom.:

Cov.:

AF XY:

0.648

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.720

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.584

AC:

88778

AN:

151942

Hom.:

26826

Cov.:

AF XY:

0.586

AC XY:

43493

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.547

AC:

22637

AN:

41406

American (AMR)

AF:

0.580

AC:

8855

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1719

AN:

3468

East Asian (EAS)

AF:

0.108

AC:

557

AN:

5148

South Asian (SAS)

AF:

0.818

AC:

3939

AN:

4816

European-Finnish (FIN)

AF:

0.611

AC:

6434

AN:

10536

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.631

AC:

42882

AN:

67982

Other (OTH)

AF:

0.547

AC:

1151

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1842

3684

5525

7367

9209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.589

Hom.:

10208

Bravo

AF:

0.566

Asia WGS

AF:

0.516

AC:

1792

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.2

(source)

DANN

Benign

0.56

PhyloP100

-2.0

PromoterAI

-0.0092

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over