rs34229137

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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:7

Conservation

PhyloP100: 0.732

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

maple syrup urine disease
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
maple syrup urine disease type 2
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P, Myriad Women’s Health
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

DBT links:

ENSG00000285530 (HGNC:):

ENSG00000285530 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DBT	NM_001918.5	MANE Select	c.1210-9A>T	intron	N/A	NP_001909.4	P11182
DBT	NM_001399969.1		c.667-9A>T	intron	N/A	NP_001386898.1	A0A7P0T9W1
DBT	NM_001399972.1		c.667-9A>T	intron	N/A	NP_001386901.1	A0A7P0T9W1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DBT	ENST00000370132.8	TSL:1 MANE Select	c.1210-9A>T	intron	N/A	ENSP00000359151.3	P11182
DBT	ENST00000681617.1		c.1336-9A>T	intron	N/A	ENSP00000505544.1	A0A7P0Z494
DBT	ENST00000875462.1		c.1210-9A>T	intron	N/A	ENSP00000545521.1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

45802

AN:

146158

Hom.:

7976

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.337

AC XY:

215012

AN XY:

638368

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13646

27291

40937

54582

68228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12156

24312

36468

48624

60780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.313

AC:

45835

AN:

146222

Hom.:

7991

Cov.:

AF XY:

0.316

AC XY:

22489

AN XY:

71150

show subpopulations

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:

AN:

288

European-Non Finnish (NFE)

AF:

0.392

AC:

26052

AN:

66478

Other (OTH)

AF:

0.340

AC:

684

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1498

2996

4493

5991

7489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.348

Hom.:

1375

Bravo

AF:

0.298

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Maple syrup urine disease (3)

not specified (3)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

(source)

DANN

Benign

0.42

PhyloP100

0.73

Mutation Taster

=60/40

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over