1-100198123-T-C

Position:

• chr1-100198123-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001918.5(DBT):​c.1282-1701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,228 control chromosomes in the GnomAD database, including 58,619 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (58619 hom., cov: 32)
• Consequence: DBT NM_001918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBT	NM_001918.5	c.1282-1701A>G		intron_variant		ENST00000370132.8	NP_001909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132.8	c.1282-1701A>G		intron_variant		1	NM_001918.5	ENSP00000359151	P1
DBT	ENST00000681617.1	c.1408-1701A>G		intron_variant				ENSP00000505544
DBT	ENST00000681780.1	c.739-1701A>G		intron_variant				ENSP00000505780

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133097 AN: 152110 Hom.: 58594 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.875 AC: 133171 AN: 152228 Hom.: 58619 Cov.: 32 AF XY: 0.879 AC XY: 65409 AN XY: 74440

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.891

Alfa AF: 0.906 Hom.: 27824

Bravo AF: 0.868

Asia WGS AF: 0.925 AC: 3216 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.63

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: rs2810424; hg19: chr1-100663679;