1-100187700-A-AT

Position:

• chr1-100187700-A-AT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001918.5(DBT):​c.*8554_*8555insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 124,128 control chromosomes in the GnomAD database, including 267 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.042 (267 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: DBT NM_001918.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -1.50

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 -9 ACMG points.

• BP6: Variant 1-100187700-A-AT is Benign according to our data. Variant chr1-100187700-A-AT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 291383.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBT	NM_001918.5	c.*8554_*8555insA		3_prime_UTR_variant	11/11	ENST00000370132.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBT	ENST00000370132.8	c.*8554_*8555insA		3_prime_UTR_variant	11/11	1	NM_001918.5	P1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 5227 AN: 124144 Hom.: 267 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00259

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.00740

Gnomad EAS AF: 0.00641

Gnomad SAS AF: 0.00423

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00802

Gnomad OTH AF: 0.0325

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: 0.0421 AC: 5232 AN: 124128 Hom.: 267 Cov.: 31 AF XY: 0.0425 AC XY: 2539 AN XY: 59798

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.00740

Gnomad4 EAS AF: 0.00643

Gnomad4 SAS AF: 0.00400

Gnomad4 FIN AF: 0.00537

Gnomad4 NFE AF: 0.00802

Gnomad4 OTH AF: 0.0318

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Maple syrup urine disease Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs886044938; hg19: chr1-100653256;