1-100235416-CT-CTT

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001918.5(DBT):c.251+19dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00897 in 1,272,154 control chromosomes in the GnomAD database, including 76 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 65 hom. )

Consequence

DBT
NM_001918.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.06

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:

ENSG00000285530 (HGNC:):

ENSG00000285530 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-100235416-C-CT is Benign according to our data. Variant chr1-100235416-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 93998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00844 (1283/152046) while in subpopulation NFE AF= 0.0134 (911/67942). AF 95% confidence interval is 0.0127. There are 11 homozygotes in gnomad4. There are 599 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5 link	c.251+19dupA		intron_variant	Intron 3 of 10	ENST00000370132.8	NP_001909.4	P11182

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132.8 link	c.251+19_251+20insA		intron_variant	Intron 3 of 10	1	NM_001918.5	ENSP00000359151.3		P11182

Frequencies

GnomAD3 genomes

AF:

0.00845

AC:

1284

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00751

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00777

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00857

AC:

2110

AN:

246188

Hom.:

AF XY:

0.00876

AC XY:

1165

AN XY:

132960

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00462

Gnomad ASJ exome

AF:

0.00726

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS exome

AF:

0.00266

Gnomad FIN exome

AF:

0.00857

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00904

AC:

10130

AN:

1120108

Hom.:

Cov.:

AF XY:

0.00916

AC XY:

5245

AN XY:

572618

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00491

Gnomad4 ASJ exome

AF:

0.00706

Gnomad4 EAS exome

AF:

0.0000265

Gnomad4 SAS exome

AF:

0.00294

Gnomad4 FIN exome

AF:

0.00927

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00825

GnomAD4 genome

AF:

0.00844

AC:

1283

AN:

152046

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

599

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00186

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00751

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00777

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.00742

Asia WGS

AF:

0.00231

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 12, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Oct 30, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Maple syrup urine disease

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Maple syrup urine disease type 1A

Benign:1

Sep 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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