4-156970791-T-C

Position:

• chr4-156970791-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016205.3(PDGFC):​c.113A>G​(p.Gln38Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00546 in 1,588,684 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (40 hom.)
• Consequence: PDGFC NM_016205.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.81

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005934298).
• BP6: Variant 4-156970791-T-C is Benign according to our data. Variant chr4-156970791-T-C is described in ClinVar as [Benign]. Clinvar id is 771707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 691 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFC	NM_016205.3	c.113A>G	p.Gln38Arg	missense_variant	1/6	ENST00000502773.6
PDGFC	NR_036641.2	n.1009A>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFC	ENST00000502773.6	c.113A>G	p.Gln38Arg	missense_variant	1/6	1	NM_016205.3	P1
PDGFC	ENST00000274071.6	c.113A>G	p.Gln38Arg	missense_variant, NMD_transcript_variant	1/7	1
PDGFC	ENST00000422544.2	c.113A>G	p.Gln38Arg	missense_variant	1/6	5
PDGFC	ENST00000513664.1	n.175A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.00454 AC: 691 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00443 AC: 1113 AN: 251412 Hom.: 5 AF XY: 0.00432 AC XY: 587 AN XY: 135886

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00379

Gnomad NFE exome AF: 0.00759

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00555 AC: 7977 AN: 1436342 Hom.: 40 Cov.: 27 AF XY: 0.00546 AC XY: 3907 AN XY: 716060

Gnomad4 AFR exome AF: 0.000910

Gnomad4 AMR exome AF: 0.00213

Gnomad4 ASJ exome AF: 0.000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000933

Gnomad4 FIN exome AF: 0.00376

Gnomad4 NFE exome AF: 0.00674

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.00454 AC: 691 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.00447 AC XY: 333 AN XY: 74492

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00764

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00661 Hom.: 6

Bravo AF: 0.00419

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00450 AC: 546

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00556

EpiControl AF: 0.00634

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.60
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.0059	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.088
Sift	Benign	0.36	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.046	B;.
Vest4		0.37
MVP		0.36
MPC		0.34
ClinPred		0.013	T
GERP RS		1.1
Varity_R		0.13
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: rs139145392; hg19: chr4-157891943;