rs201755806

chr1-100206309-T-TAchr1-100206309-T-TAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001918.5(DBT):c.1210-9_1210-8insT variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.732

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]

ACMG classification

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 GnomAdExome at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBT	NM_001918.5	c.1210-9_1210-8insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000370132.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBT	ENST00000370132.8	c.1210-9_1210-8insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001918.5	P1
DBT	ENST00000681617.1	c.1336-9_1336-8insT		splice_polypyrimidine_tract_variant, intron_variant
DBT	ENST00000681780.1	c.667-9_667-8insT		splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.000188 AC: 28 AN: 148728 Hom.: 0 Cov.: 29

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.: 12 AF XY: 0.0112 AC XY: 1273 AN XY: 113472

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.: 11 Cov.: 29 AF XY: 0.0183 AC XY: 11378 AN XY: 621670

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: 30 AN: 148830 Hom.: 0 Cov.: 29 AF XY: 0.000276 AC XY: 20 AN XY: 72452

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.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

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

Maple syrup urine disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs201755806; hg19: chr1-100671865; COSMIC: COSV64496203; COSMIC: COSV64496203;