rs115696850

Variant names:

• chr1-100206199-A-C
• rs115696850
• NM_001918.5:c.1281+31T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001918.5(DBT):​c.1281+31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,508,738 control chromosomes in the GnomAD database, including 1,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (92 hom., cov: 30)
  • Exomes 𝑓: 0.041 (1374 hom.)
• Consequence: DBT NM_001918.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.52

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-100206199-A-C is Benign according to our data. Variant chr1-100206199-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 93989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0299 (4545/152060) while in subpopulation NFE AF = 0.0449 (3054/67992). AF 95% confidence interval is 0.0436. There are 92 homozygotes in GnomAd4. There are 2169 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 92 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5	c.1281+31T>G		intron_variant	Intron 10 of 10	ENST00000370132.8	NP_001909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132.8	c.1281+31T>G		intron_variant	Intron 10 of 10	1	NM_001918.5	ENSP00000359151.3
DBT	ENST00000681617.1	c.1407+31T>G		intron_variant	Intron 11 of 11			ENSP00000505544.1
DBT	ENST00000681780.1	c.738+31T>G		intron_variant	Intron 11 of 11			ENSP00000505780.1

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4545 AN: 151944 Hom.: 92 Cov.: 30

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.0268

GnomAD2 exomes AF: 0.0317 AC: 7869 AN: 248570 AF XY: 0.0330

Gnomad AFR exome AF: 0.00697

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0423

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.0465

Gnomad OTH exome AF: 0.0347

GnomAD4 exome AF: 0.0407 AC: 55213 AN: 1356678 Hom.: 1374 Cov.: 20 AF XY: 0.0401 AC XY: 27293 AN XY: 680782

Gnomad4 AFR exome AF: 0.00725 AC: 227 AN: 31292

Gnomad4 AMR exome AF: 0.0189 AC: 832 AN: 44130

Gnomad4 ASJ exome AF: 0.0419 AC: 1069 AN: 25492

Gnomad4 EAS exome AF: 0.0000255 AC: 1 AN: 39190

Gnomad4 SAS exome AF: 0.0104 AC: 866 AN: 83012

Gnomad4 FIN exome AF: 0.0433 AC: 2308 AN: 53304

Gnomad4 NFE exome AF: 0.0468 AC: 47637 AN: 1017858

Gnomad4 Remaining exome AF: 0.0356 AC: 2024 AN: 56834

GnomAD4 genome AF: 0.0299 AC: 4545 AN: 152060 Hom.: 92 Cov.: 30 AF XY: 0.0292 AC XY: 2169 AN XY: 74342

Gnomad4 AFR AF: 0.00803 AC: 0.00802874 AN: 0.00802874

Gnomad4 AMR AF: 0.0246 AC: 0.0246428 AN: 0.0246428

Gnomad4 ASJ AF: 0.0484 AC: 0.048415 AN: 0.048415

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.0114 AC: 0.0114108 AN: 0.0114108

Gnomad4 FIN AF: 0.0438 AC: 0.0437832 AN: 0.0437832

Gnomad4 NFE AF: 0.0449 AC: 0.044917 AN: 0.044917

Gnomad4 OTH AF: 0.0266 AC: 0.0265655 AN: 0.0265655

Alfa AF: 0.0360 Hom.: 16

Bravo AF: 0.0290

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 23, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jun 23, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Maple syrup urine disease Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs115696850; hg19: chr1-100671755;