rs1002091

Variant names:

• chr4-156972019-C-G
• rs1002091
• NM_016205.3:c.-1116G>C

Variant summary

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

The NM_016205.3(PDGFC):​c.-1116G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,012 control chromosomes in the GnomAD database, including 28,889 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 0.61 (28889 hom., cov: 34)
• Consequence: PDGFC NM_016205.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.-1116G>C		upstream_gene_variant		ENST00000502773.6	NP_057289.1
PDGFC	NR_036641.2	n.-220G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773.6	c.-1116G>C		upstream_gene_variant		1	NM_016205.3	ENSP00000422464.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92616 AN: 151898 Hom.: 28880 Cov.: 34

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.610 AC: 92654 AN: 152012 Hom.: 28889 Cov.: 34 AF XY: 0.604 AC XY: 44850 AN XY: 74286

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.652

Alfa AF: 0.643 Hom.: 3983

Bravo AF: 0.610

Asia WGS AF: 0.520 AC: 1811 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1002091; hg19: chr4-157893171;