16-31113086-A-G

Position:

• chr16-31113086-A-G

Variant summary

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

The XM_017022859.2(BCKDK):​c.1094+1059A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,206 control chromosomes in the GnomAD database, including 11,355 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 0.37 (11355 hom., cov: 33)
• Consequence: BCKDK XM_017022859.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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
BCKDK	XM_017022859.2	c.1094+1059A>G		intron_variant			XP_016878348.1
		n.31113086A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.368 AC: 56005 AN: 152088 Hom.: 11356 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.368 AC: 56013 AN: 152206 Hom.: 11355 Cov.: 33 AF XY: 0.369 AC XY: 27422 AN XY: 74414

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.422

Alfa AF: 0.376 Hom.: 6983

Bravo AF: 0.379

Asia WGS AF: 0.470 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs749767; hg19: chr16-31124407;