Genetic Variant DBT:c.*8554dupA (chr1-100187700-A-AT) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_001918.5(DBT):c.*8554dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 124,128 control chromosomes in the GnomAD database, including 267 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.042 ( 267 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

DBT
NM_001918.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

DBT (HGNC:2698): (dihydrolipoamide branched chain transacylase E2) The branched-chain alpha-keto acid dehydrogenase complex (BCKD) is an inner-mitochondrial enzyme complex involved in the breakdown of the branched-chain amino acids isoleucine, leucine, and valine. The BCKD complex is thought to be composed of a core of 24 transacylase (E2) subunits, and associated decarboxylase (E1), dehydrogenase (E3), and regulatory subunits. This gene encodes the transacylase (E2) subunit. Mutations in this gene result in maple syrup urine disease, type 2. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

DBT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 1-100187700-A-AT is Benign according to our data. Variant chr1-100187700-A-AT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 291383.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5 link	c.*8554dupA		3_prime_UTR_variant	Exon 11 of 11	ENST00000370132.8	NP_001909.4	P11182

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132 link	c.*8554dupA		3_prime_UTR_variant	Exon 11 of 11	1	NM_001918.5	ENSP00000359151.3		P11182

Frequencies

GnomAD3 genomes

AF:

0.0421

AC:

5227

AN:

124144

Hom.:

267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.00259

Gnomad AMR

AF:

0.0350

Gnomad ASJ

AF:

0.00740

Gnomad EAS

AF:

0.00641

Gnomad SAS

AF:

0.00423

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00802

Gnomad OTH

AF:

0.0325

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AC:

AN:

Gnomad4 NFE exome

AC:

AN:

Gnomad4 Remaining exome

AC:

AN:

GnomAD4 genome

AF:

0.0421

AC:

5232

AN:

124128

Hom.:

267

Cov.:

AF XY:

0.0425

AC XY:

2539

AN XY:

59798

show subpopulations

Gnomad4 AFR

AF:

0.124

AC:

0.123763

AN:

0.123763

Gnomad4 AMR

AF:

0.0351

AC:

0.0350735

AN:

0.0350735

Gnomad4 ASJ

AF:

0.00740

AC:

0.00739744

AN:

0.00739744

Gnomad4 EAS

AF:

0.00643

AC:

0.00642857

AN:

0.00642857

Gnomad4 SAS

AF:

0.00400

AC:

0.003998

AN:

0.003998

Gnomad4 FIN

AF:

0.00537

AC:

0.00537322

AN:

0.00537322

Gnomad4 NFE

AF:

0.00802

AC:

0.00802307

AN:

0.00802307

Gnomad4 OTH

AF:

0.0318

AC:

0.0317919

AN:

0.0317919

Heterozygous variant carriers

223

446

668

891

1114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.000285

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Maple syrup urine disease

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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