rs4691380

Positions:

• chr4-156798972-C-T

Variant summary

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

The NM_016205.3(PDGFC):​c.495+11865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,014 control chromosomes in the GnomAD database, including 17,876 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 0.45 (17876 hom., cov: 32)
• Consequence: PDGFC NM_016205.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

Genes affected

PDGFC (HGNC:8801): (platelet derived growth factor C) The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines. This gene product appears to form only homodimers. It differs from the platelet-derived growth factor alpha and beta polypeptides in having an unusual N-terminal domain, the CUB domain. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.495+11865G>A		intron_variant		ENST00000502773.6	NP_057289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773.6	c.495+11865G>A		intron_variant		1	NM_016205.3	ENSP00000422464	P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68137 AN: 151896 Hom.: 17829 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.449 AC: 68243 AN: 152014 Hom.: 17876 Cov.: 32 AF XY: 0.446 AC XY: 33158 AN XY: 74266

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.441

Alfa AF: 0.351 Hom.: 11812

Bravo AF: 0.466

Asia WGS AF: 0.466 AC: 1618 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.66
DANN	Benign	0.33

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: rs4691380; hg19: chr4-157720124;