4-156763096-T-C

Variant names:

• chr4-156763096-T-C
• rs3815861
• NM_016205.3:c.1032A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016205.3(PDGFC):​c.1032A>G​(p.Gly344Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,567,192 control chromosomes in the GnomAD database, including 25,106 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 0.18 (2520 hom., cov: 31)
  • Exomes 𝑓: 0.17 (22586 hom.)
• Consequence: PDGFC NM_016205.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 15 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.339 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016205.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFC	NM_016205.3	MANE Select	c.1032A>G	p.Gly344Gly	synonymous	Exon 6 of 6	NP_057289.1
	PDGFC	NR_036641.2		n.1989A>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFC	ENST00000502773.6	TSL:1 MANE Select	c.1032A>G	p.Gly344Gly	synonymous	Exon 6 of 6	ENSP00000422464.1
	PDGFC	ENST00000274071.6	TSL:1	n.*940A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000274071.2
	PDGFC	ENST00000274071.6	TSL:1	n.*940A>G		3_prime_UTR	Exon 7 of 7	ENSP00000274071.2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26794 AN: 151910 Hom.: 2520 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0859

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.194 AC: 48620 AN: 250764 AF XY: 0.202

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.172

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.168 AC: 237480 AN: 1415164 Hom.: 22586 Cov.: 26 AF XY: 0.174 AC XY: 123281 AN XY: 706936

African (AFR) AF: 0.199 AC: 6464 AN: 32468

American (AMR) AF: 0.196 AC: 8741 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3593 AN: 25836

East Asian (EAS) AF: 0.179 AC: 7055 AN: 39500

South Asian (SAS) AF: 0.383 AC: 32590 AN: 85156

European-Finnish (FIN) AF: 0.160 AC: 8561 AN: 53382

Middle Eastern (MID) AF: 0.217 AC: 1228 AN: 5656

European-Non Finnish (NFE) AF: 0.149 AC: 159387 AN: 1069688

Other (OTH) AF: 0.168 AC: 9861 AN: 58812

GnomAD4 genome AF: 0.176 AC: 26806 AN: 152028 Hom.: 2520 Cov.: 31 AF XY: 0.180 AC XY: 13380 AN XY: 74304

African (AFR) AF: 0.204 AC: 8453 AN: 41478

American (AMR) AF: 0.160 AC: 2441 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.163 AC: 842 AN: 5150

South Asian (SAS) AF: 0.400 AC: 1928 AN: 4816

European-Finnish (FIN) AF: 0.160 AC: 1693 AN: 10570

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.155 AC: 10505 AN: 67972

Other (OTH) AF: 0.167 AC: 351 AN: 2108

Alfa AF: 0.149 Hom.: 1409

Bravo AF: 0.172

Asia WGS AF: 0.274 AC: 950 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.8
DANN	Benign	0.69
PhyloP100		0.34
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: rs3815861; hg19: chr4-157684248; COSMIC: COSV56845002; COSMIC: COSV56845002;