rs1425486

Positions:

• chr4-156762533-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016205.3(PDGFC):​c.*557G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,456 control chromosomes in the GnomAD database, including 19,122 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 0.46 (19122 hom., cov: 30)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: PDGFC NM_016205.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.*557G>A		3_prime_UTR_variant	6/6	ENST00000502773.6	NP_057289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773	c.*557G>A		3_prime_UTR_variant	6/6	1	NM_016205.3	ENSP00000422464.1
PDGFC	ENST00000274071.6	n.*1503G>A		non_coding_transcript_exon_variant	7/7	1		ENSP00000274071.2
PDGFC	ENST00000274071.6	n.*1503G>A		3_prime_UTR_variant	7/7	1		ENSP00000274071.2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69538 AN: 151288 Hom.: 19073 Cov.: 30

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.304 AC: 14 AN: 46 Hom.: 0 Cov.: 0 AF XY: 0.357 AC XY: 10 AN XY: 28

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.400

GnomAD4 genome AF: 0.460 AC: 69643 AN: 151410 Hom.: 19122 Cov.: 30 AF XY: 0.458 AC XY: 33819 AN XY: 73892

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.452

Alfa AF: 0.369 Hom.: 10631

Bravo AF: 0.478

Asia WGS AF: 0.487 AC: 1690 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.62

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: rs1425486; hg19: chr4-157683685;