16-31106092-C-T

Position:

• chr16-31106092-C-T

Variant summary

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

The variant allele was found at a frequency of 0.302 in 152,168 control chromosomes in the GnomAD database, including 9,414 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 0.30 (9413 hom., cov: 32)
  • Exomes 𝑓: 0.37 (1 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

Genes affected

(HGNC:):

BCKDK (HGNC:16902): (branched chain keto acid dehydrogenase kinase) The branched-chain alpha-ketoacid dehydrogenase complex (BCKD) is an important regulator of the valine, leucine, and isoleucine catabolic pathways. The protein encoded by this gene is found in the mitochondrion, where it phosphorylates and inactivates BCKD. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.31106092C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCKDK	ENST00000394951.5	c.-638C>T		upstream_gene_variant		5		ENSP00000378405.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45970 AN: 152022 Hom.: 9412 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.367 AC: 11 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.385 AC XY: 10 AN XY: 26

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.302 AC: 45970 AN: 152138 Hom.: 9413 Cov.: 32 AF XY: 0.305 AC XY: 22716 AN XY: 74358

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.368

Alfa AF: 0.368 Hom.: 4005

Bravo AF: 0.304

Asia WGS AF: 0.455 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.1
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2032915; hg19: chr16-31117413;