1-100187700-ATTTTTTT-ATTTTT

Variant names:

• chr1-100187700-ATT-A
• rs886044938
• NM_001918.5:c.*8553_*8554delAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001918.5(DBT):​c.*8553_*8554delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000733 in 124,092 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: DBT NM_001918.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000733 (91/124092) while in subpopulation EAS AF= 0.0148 (62/4202). AF 95% confidence interval is 0.0118. There are 1 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5	c.*8553_*8554delAA		3_prime_UTR_variant	Exon 11 of 11	ENST00000370132.8	NP_001909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132	c.*8553_*8554delAA		3_prime_UTR_variant	Exon 11 of 11	1	NM_001918.5	ENSP00000359151.3

Frequencies

GnomAD3 genomes AF: 0.000741 AC: 92 AN: 124108 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000162

Gnomad ASJ AF: 0.000336

Gnomad EAS AF: 0.0149

Gnomad SAS AF: 0.000995

Gnomad FIN AF: 0.000437

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000175

Gnomad OTH AF: 0.00233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000733 AC: 91 AN: 124092 Hom.: 1 Cov.: 31 AF XY: 0.000803 AC XY: 48 AN XY: 59778

Gnomad4 AFR AF: 0.000148

Gnomad4 AMR AF: 0.000162

Gnomad4 ASJ AF: 0.000336

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.000999

Gnomad4 FIN AF: 0.000437

Gnomad4 NFE AF: 0.000175

Gnomad4 OTH AF: 0.00232

ClinVar

Not reported in ClinVar

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;