NM_016205.3:c.496-1347G>A

Variant names:

• chr4-156774240-C-T
• rs983473
• NM_016205.3:c.496-1347G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016205.3(PDGFC):​c.496-1347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,002 control chromosomes in the GnomAD database, including 8,206 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 0.31 (8205 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: PDGFC NM_016205.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.496-1347G>A		intron_variant	Intron 3 of 5	ENST00000502773.6	NP_057289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773.6	c.496-1347G>A		intron_variant	Intron 3 of 5	1	NM_016205.3	ENSP00000422464.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46606 AN: 151866 Hom.: 8182 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.167 AC: 3 AN: 18 Hom.: 1 AF XY: 0.214 AC XY: 3 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 3 AN: 18

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.307 AC: 46670 AN: 151984 Hom.: 8205 Cov.: 32 AF XY: 0.307 AC XY: 22843 AN XY: 74288

African (AFR) AF: 0.464 AC: 19224 AN: 41424

American (AMR) AF: 0.274 AC: 4185 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1139 AN: 5152

South Asian (SAS) AF: 0.548 AC: 2630 AN: 4800

European-Finnish (FIN) AF: 0.193 AC: 2045 AN: 10584

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15731 AN: 67970

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.258 Hom.: 9241

Bravo AF: 0.315

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		1.4
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: rs983473; hg19: chr4-157695392;