1-100187700-AT-A

Position:

• chr1-100187700-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001918.5(DBT):​c.*8554del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 124,068 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0093 (5 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: DBT NM_001918.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter 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 -10 ACMG points.

• BP6: Variant 1-100187700-AT-A is Benign according to our data. Variant chr1-100187700-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1195364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00925 (1148/124068) while in subpopulation SAS AF= 0.012 (48/4002). AF 95% confidence interval is 0.0101. There are 5 homozygotes in gnomad4. There are 544 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00924 AC: 1146 AN: 124084 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00640

Gnomad EAS AF: 0.00214

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0168

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: 0.00925 AC: 1148 AN: 124068 Hom.: 5 Cov.: 31 AF XY: 0.00910 AC XY: 544 AN XY: 59774

Gnomad4 AFR AF: 0.00513

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00640

Gnomad4 EAS AF: 0.00214

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0168

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2020

- -

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;