Variant rs201755806 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001918.5(DBT):c.1210-9_1210-8insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,394,356 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 29)

Exomes 𝑓: 0.019 ( 11 hom. )

Consequence

DBT
NM_001918.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.732

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:

DBT (HGNC:):

DBT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-100206309-T-TA is Benign according to our data. Variant chr1-100206309-T-TA is described in ClinVar as [Benign]. Clinvar id is 457146.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0193 (24056/1245526) while in subpopulation AMR AF= 0.0212 (791/37230). AF 95% confidence interval is 0.021. There are 11 homozygotes in gnomad4_exome. There are 11378 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBT	NM_001918.5 linkuse as main transcript	c.1210-9_1210-8insT		intron_variant		ENST00000370132.8	NP_001909.4	P11182

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DBT	ENST00000370132.8 linkuse as main transcript	c.1210-9_1210-8insT	intron_variant	1	NM_001918.5	ENSP00000359151.3	P11182
DBT	ENST00000681617.1 linkuse as main transcript	c.1336-9_1336-8insT	intron_variant			ENSP00000505544.1	A0A7P0Z494
DBT	ENST00000681780.1 linkuse as main transcript	c.667-9_667-8insT	intron_variant			ENSP00000505780.1	A0A7P0T9W1

Frequencies

GnomAD3 genomes

AF:

0.000188

AC:

AN:

148728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.000845

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0117

AC:

2434

AN:

208398

Hom.:

AF XY:

0.0112

AC XY:

1273

AN XY:

113472

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.0208

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00481

Gnomad SAS exome

AF:

0.00840

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.0193

AC:

24056

AN:

1245526

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

11378

AN XY:

621670

show subpopulations

Gnomad4 AFR exome

AF:

0.00274

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.00958

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0212

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.000202

AC:

AN:

148830

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

AN XY:

72452

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.000401

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.000845

Gnomad4 NFE

AF:

0.000208

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0167

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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