4-156767839-G-C

Position:

• chr4-156767839-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_016205.3(PDGFC):​c.855C>G​(p.Ala285=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00342 in 1,613,346 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (68 hom.)
• Consequence: PDGFC NM_016205.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.80

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 4-156767839-G-C is Benign according to our data. Variant chr4-156767839-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 715728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 674 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFC	NM_016205.3	c.855C>G	p.Ala285=	synonymous_variant	5/6	ENST00000502773.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFC	ENST00000502773.6	c.855C>G	p.Ala285=	synonymous_variant	5/6	1	NM_016205.3	P1

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 674 AN: 151944 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00425

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00512 AC: 1286 AN: 251074 Hom.: 19 AF XY: 0.00470 AC XY: 638 AN XY: 135674

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00606

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0307

Gnomad NFE exome AF: 0.00456

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00331 AC: 4840 AN: 1461284 Hom.: 68 Cov.: 31 AF XY: 0.00329 AC XY: 2388 AN XY: 726928

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00586

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0336

Gnomad4 NFE exome AF: 0.00243

Gnomad4 OTH exome AF: 0.00268

GnomAD4 genome AF: 0.00443 AC: 674 AN: 152062 Hom.: 9 Cov.: 32 AF XY: 0.00519 AC XY: 386 AN XY: 74324

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000852

Gnomad4 ASJ AF: 0.00664

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.00425

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00413 Hom.: 0

Bravo AF: 0.00197

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00267

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	PDGFC: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.5
DANN	Benign	0.68

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: rs142817291; hg19: chr4-157688991;