rs34229137

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• maple syrup urine disease

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• maple syrup urine disease type 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, G2P
• classic maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intermediate maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intermittent maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• thiamine-responsive maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285530 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.
• 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
ENSG00000285530	ENST00000835180.1	n.140-12334T>A		intron_variant	Intron 2 of 4

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

GnomAD2 exomes AF: 0.400 AC: 69673 AN: 173974 AF XY: 0.399

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.328

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.418

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

African (AFR) AF: 0.122 AC: 3439 AN: 28190

American (AMR) AF: 0.371 AC: 14688 AN: 39642

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 6950 AN: 23106

East Asian (EAS) AF: 0.259 AC: 9148 AN: 35330

South Asian (SAS) AF: 0.292 AC: 22624 AN: 77500

European-Finnish (FIN) AF: 0.356 AC: 16774 AN: 47116

Middle Eastern (MID) AF: 0.252 AC: 1280 AN: 5082

European-Non Finnish (NFE) AF: 0.353 AC: 341954 AN: 968232

Other (OTH) AF: 0.322 AC: 17119 AN: 53152

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

African (AFR) AF: 0.128 AC: 5036 AN: 39370

American (AMR) AF: 0.385 AC: 5678 AN: 14750

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1108 AN: 3408

East Asian (EAS) AF: 0.253 AC: 1273 AN: 5028

South Asian (SAS) AF: 0.337 AC: 1550 AN: 4600

European-Finnish (FIN) AF: 0.429 AC: 4031 AN: 9388

Middle Eastern (MID) AF: 0.316 AC: 91 AN: 288

European-Non Finnish (NFE) AF: 0.392 AC: 26052 AN: 66478

Other (OTH) AF: 0.340 AC: 684 AN: 2014

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

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
PhyloP100		0.73
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

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