rs2301630

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002612.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK4	NM_002612.4	MANE Select	c.694+31G>A		intron	N/A	NP_002603.1	A4D1H4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK4	ENST00000005178.6	TSL:1 MANE Select	c.694+31G>A		intron	N/A	ENSP00000005178.5	Q16654
	PDK4	ENST00000886049.1		c.694+31G>A		intron	N/A	ENSP00000556108.1
	PDK4	ENST00000886050.1		c.688+31G>A		intron	N/A	ENSP00000556109.1

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

GnomAD2 exomes AF: 0.499 AC: 92370 AN: 185222 AF XY: 0.504

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 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

African (AFR) AF: 0.612 AC: 11952 AN: 19538

American (AMR) AF: 0.404 AC: 10955 AN: 27134

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 10977 AN: 21286

East Asian (EAS) AF: 0.887 AC: 28353 AN: 31976

South Asian (SAS) AF: 0.685 AC: 43152 AN: 62982

European-Finnish (FIN) AF: 0.435 AC: 22704 AN: 52214

Middle Eastern (MID) AF: 0.575 AC: 2464 AN: 4282

European-Non Finnish (NFE) AF: 0.421 AC: 290987 AN: 691842

Other (OTH) AF: 0.490 AC: 20981 AN: 42792

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

African (AFR) AF: 0.622 AC: 25751 AN: 41412

American (AMR) AF: 0.429 AC: 6548 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3470

East Asian (EAS) AF: 0.925 AC: 4787 AN: 5176

South Asian (SAS) AF: 0.700 AC: 3377 AN: 4822

European-Finnish (FIN) AF: 0.438 AC: 4623 AN: 10552

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29401 AN: 67912

Other (OTH) AF: 0.521 AC: 1098 AN: 2108

Alfa AF: 0.482 Hom.: 8644

Bravo AF: 0.512

Asia WGS AF: 0.777 AC: 2678 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.58
PhyloP100		-0.049
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301630; hg19: chr7-95221269;