rs56314408

Positions:

• chr16-31106068-T-C

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 0.584 in 152,002 control chromosomes in the GnomAD database, including 26,840 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 0.58 (26826 hom., cov: 32)
  • Exomes 𝑓: 0.68 (14 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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 (SAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.31106068T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCKDK	ENST00000394951.5	c.-662T>C		upstream_gene_variant		5		ENSP00000378405.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88688 AN: 151824 Hom.: 26792 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.683 AC: 41 AN: 60 Hom.: 14 Cov.: 0 AF XY: 0.648 AC XY: 35 AN XY: 54

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.584 AC: 88778 AN: 151942 Hom.: 26826 Cov.: 32 AF XY: 0.586 AC XY: 43493 AN XY: 74258

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.547

Alfa AF: 0.594 Hom.: 9549

Bravo AF: 0.566

Asia WGS AF: 0.516 AC: 1792 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	1.2
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56314408; hg19: chr16-31117389;