Variant chr1-100206304-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001918.5(DBT):c.1210-4dupA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,436,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

DBT
NM_001918.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.564

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 1-100206304-A-AT is Benign according to our data. Variant chr1-100206304-A-AT is described in ClinVar as [Benign]. Clinvar id is 457145.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBT	NM_001918.5 linkuse as main transcript	c.1210-4dupA		splice_region_variant, 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.1210-4dupA	splice_region_variant, intron_variant	1	NM_001918.5	ENSP00000359151.3	P11182
DBT	ENST00000681617.1 linkuse as main transcript	c.1336-4dupA	splice_region_variant, intron_variant			ENSP00000505544.1	A0A7P0Z494
DBT	ENST00000681780.1 linkuse as main transcript	c.667-4dupA	splice_region_variant, intron_variant			ENSP00000505780.1	A0A7P0T9W1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

148698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000595

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000471

AC:

607

AN:

1287388

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

311

AN XY:

642856

show subpopulations

Gnomad4 AFR exome

AF:

0.000219

Gnomad4 AMR exome

AF:

0.000126

Gnomad4 ASJ exome

AF:

0.000557

Gnomad4 EAS exome

AF:

0.000137

Gnomad4 SAS exome

AF:

0.000482

Gnomad4 FIN exome

AF:

0.000362

Gnomad4 NFE exome

AF:

0.000510

Gnomad4 OTH exome

AF:

0.000465

GnomAD4 genome

AF:

0.0000269

AC:

AN:

148796

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

72550

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000596

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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