rs2301630

Variant names:

• chr7-95591957-C-T
• rs2301630
• NM_002612.4:c.694+31G>A

Variant summary

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

The NM_002612.4(PDK4):​c.694+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,105,972 control chromosomes in the GnomAD database, including 129,998 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 0.51 (20877 hom., cov: 32)
  • Exomes 𝑓: 0.46 (109121 hom.)
• Consequence: PDK4 NM_002612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

PDK4 (HGNC:8812): (pyruvate dehydrogenase kinase 4) This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. [provided by RefSeq, Jul 2008]

PDK4-AS1 (HGNC:55767): (PDK4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK4	NM_002612.4	c.694+31G>A		intron_variant	Intron 6 of 10	ENST00000005178.6	NP_002603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK4	ENST00000005178.6	c.694+31G>A		intron_variant	Intron 6 of 10	1	NM_002612.4	ENSP00000005178.5

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77768 AN: 151808 Hom.: 20853 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.520

GnomAD3 exomes AF: 0.499 AC: 92370 AN: 185222 Hom.: 25036 AF XY: 0.504 AC XY: 51602 AN XY: 102308

Gnomad AFR exome AF: 0.613

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.508

Gnomad EAS exome AF: 0.930

Gnomad SAS exome AF: 0.686

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.464 AC: 442525 AN: 954046 Hom.: 109121 Cov.: 12 AF XY: 0.471 AC XY: 232157 AN XY: 492914

Gnomad4 AFR exome AF: 0.612

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.887

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.512 AC: 77830 AN: 151926 Hom.: 20877 Cov.: 32 AF XY: 0.518 AC XY: 38508 AN XY: 74294

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.521

Alfa AF: 0.463 Hom.: 5043

Bravo AF: 0.512

Asia WGS AF: 0.777 AC: 2678 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.58

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: rs2301630; hg19: chr7-95221269;