1-100187173-G-A

Position:

• chr1-100187173-G-A

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.*9082C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,132 control chromosomes in the GnomAD database, including 1,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1397 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DBT NM_001918.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.326

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-100187173-G-A is Benign according to our data. Variant chr1-100187173-G-A is described in ClinVar as [Benign]. Clinvar id is 291375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBT	NM_001918.5	c.*9082C>T		3_prime_UTR_variant	11/11	ENST00000370132.8	NP_001909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132	c.*9082C>T		3_prime_UTR_variant	11/11	1	NM_001918.5	ENSP00000359151.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17822 AN: 152014 Hom.: 1396 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.140

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.117 AC: 17822 AN: 152132 Hom.: 1397 Cov.: 32 AF XY: 0.113 AC XY: 8408 AN XY: 74350

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.138

Alfa AF: 0.154 Hom.: 388

Bravo AF: 0.113

Asia WGS AF: 0.0240 AC: 84 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maple syrup urine disease Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.1
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs72728160; hg19: chr1-100652729;