rs115696850

chr1-100206199-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001918.5(DBT):c.1281+31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,508,738 control chromosomes in the GnomAD database, including 1,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 92 hom., cov: 30)

Exomes 𝑓: 0.041 ( 1374 hom. )

Consequence

DBT
NM_001918.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.52

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-100206199-A-C is Benign according to our data. Variant chr1-100206199-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 93989.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 = 0.0299 (4545/152060) while in subpopulation NFE AF= 0.0449 (3054/67992). AF 95% confidence interval is 0.0436. There are 92 homozygotes in gnomad4. There are 2169 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 92 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBT	NM_001918.5 linkuse as main transcript	c.1281+31T>G		intron_variant		ENST00000370132.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
DBT	ENST00000370132.8 linkuse as main transcript	c.1281+31T>G	intron_variant	1	NM_001918.5	P1
DBT	ENST00000681617.1 linkuse as main transcript	c.1407+31T>G	intron_variant
DBT	ENST00000681780.1 linkuse as main transcript	c.738+31T>G	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4545

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00805

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0438

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0317

AC:

7869

AN:

248570

Hom.:

186

AF XY:

0.0330

AC XY:

4422

AN XY:

134132

show subpopulations

Gnomad AFR exome

AF:

0.00697

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0423

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0465

Gnomad OTH exome

AF:

0.0347

GnomAD4 exome

AF:

0.0407

AC:

55213

AN:

1356678

Hom.:

1374

Cov.:

AF XY:

0.0401

AC XY:

27293

AN XY:

680782

show subpopulations

Gnomad4 AFR exome

AF:

0.00725

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.0419

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.0433

Gnomad4 NFE exome

AF:

0.0468

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0299

AC:

4545

AN:

152060

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

2169

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00803

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.0484

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0438

Gnomad4 NFE

AF:

0.0449

Gnomad4 OTH

AF:

0.0266

Alfa

AF:

0.0360

Hom.:

Bravo

AF:

0.0290

Asia WGS

AF:

0.00549

AC:

AN:

3476

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

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 23, 2013	- -

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

6.4

Dann

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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