rs34229137

Variant names:

• chr1-100206310-T-A
• rs34229137
• NM_001918.5:c.1210-9A>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001918.5(DBT):​c.1210-9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,423,572 control chromosomes in the GnomAD database, including 33,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7991 hom., cov: 29)
  • Exomes 𝑓: 0.34 (25446 hom.)
• Consequence: DBT NM_001918.5 intron
• Scores: Splicing: ADA: 0.000004809
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-100206310-T-A is Benign according to our data. Variant chr1-100206310-T-A is described in ClinVar as [Benign]. Clinvar id is 93987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-100206310-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5	c.1210-9A>T		intron_variant	Intron 9 of 10	ENST00000370132.8	NP_001909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132.8	c.1210-9A>T		intron_variant	Intron 9 of 10	1	NM_001918.5	ENSP00000359151.3
DBT	ENST00000681617.1	c.1336-9A>T		intron_variant	Intron 10 of 11			ENSP00000505544.1
DBT	ENST00000681780.1	c.667-9A>T		intron_variant	Intron 10 of 11			ENSP00000505780.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 45802 AN: 146158 Hom.: 7976 Cov.: 29

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.340 AC: 433976 AN: 1277350 Hom.: 25446 Cov.: 29 AF XY: 0.337 AC XY: 215012 AN XY: 638368

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.313 AC: 45835 AN: 146222 Hom.: 7991 Cov.: 29 AF XY: 0.316 AC XY: 22489 AN XY: 71150

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.340

Alfa AF: 0.348 Hom.: 1375

Bravo AF: 0.298

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maple syrup urine disease Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Sep 18, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000048
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs34229137; hg19: chr1-100671866; COSMIC: COSV64495481; COSMIC: COSV64495481;