chr4-156970811-C-A

Position:

• chr4-156970811-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016205.3(PDGFC):​c.93G>T​(p.Gln31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,611,858 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (15 hom.)
• Consequence: PDGFC NM_016205.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.82

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040890574).
• BP6: Variant 4-156970811-C-A is Benign according to our data. Variant chr4-156970811-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 470 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFC	NM_016205.3	c.93G>T	p.Gln31His	missense_variant	1/6	ENST00000502773.6
PDGFC	NR_036641.2	n.989G>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFC	ENST00000502773.6	c.93G>T	p.Gln31His	missense_variant	1/6	1	NM_016205.3	P1
PDGFC	ENST00000274071.6	c.93G>T	p.Gln31His	missense_variant, NMD_transcript_variant	1/7	1
PDGFC	ENST00000422544.2	c.93G>T	p.Gln31His	missense_variant	1/6	5
PDGFC	ENST00000513664.1	n.155G>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00548

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00276 AC: 693 AN: 251442 Hom.: 1 AF XY: 0.00269 AC XY: 365 AN XY: 135908

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00484

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00427

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00405 AC: 5914 AN: 1459578 Hom.: 15 Cov.: 30 AF XY: 0.00408 AC XY: 2965 AN XY: 726286

Gnomad4 AFR exome AF: 0.000419

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.000421

Gnomad4 EAS exome AF: 0.00675

Gnomad4 SAS exome AF: 0.000835

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.00463

Gnomad4 OTH exome AF: 0.00403

GnomAD4 genome AF: 0.00309 AC: 470 AN: 152280 Hom.: 1 Cov.: 32 AF XY: 0.00271 AC XY: 202 AN XY: 74432

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00464

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00548

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00416 Hom.: 3

Bravo AF: 0.00284

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00407 AC: 35

ExAC AF: 0.00282 AC: 342

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00414

EpiControl AF: 0.00421

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PDGFC-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 13, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.60
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.094
Sift	Benign	0.22	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0	B;.
Vest4		0.13
MutPred		0.30		Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);
MVP		0.18
MPC		0.29
ClinPred		0.012	T
GERP RS		5.1
Varity_R		0.17
gMVP		0.47

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: rs149931440; hg19: chr4-157891963; COSMIC: COSV56849125; COSMIC: COSV56849125;