rs28999109

Variant names:

• chr4-156971889-G-A
• rs28999109
• NM_016205.3:c.-986C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016205.3(PDGFC):​c.-986C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 152,038 control chromosomes in the GnomAD database, including 581 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 0.078 (581 hom., cov: 32)
• Consequence: PDGFC NM_016205.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.-986C>T		upstream_gene_variant		ENST00000502773.6	NP_057289.1
PDGFC	NR_036641.2	n.-90C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773.6	c.-986C>T		upstream_gene_variant		1	NM_016205.3	ENSP00000422464.1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11834 AN: 151932 Hom.: 579 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0859

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

GnomAD4 genome AF: 0.0779 AC: 11838 AN: 152038 Hom.: 581 Cov.: 32 AF XY: 0.0762 AC XY: 5664 AN XY: 74308

African (AFR) AF: 0.0198 AC: 821 AN: 41536

American (AMR) AF: 0.0797 AC: 1218 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3470

East Asian (EAS) AF: 0.0474 AC: 242 AN: 5106

South Asian (SAS) AF: 0.0482 AC: 233 AN: 4830

European-Finnish (FIN) AF: 0.0888 AC: 939 AN: 10580

Middle Eastern (MID) AF: 0.0690 AC: 20 AN: 290

European-Non Finnish (NFE) AF: 0.113 AC: 7668 AN: 67924

Other (OTH) AF: 0.0883 AC: 186 AN: 2106

Alfa AF: 0.0967 Hom.: 91

Bravo AF: 0.0759

Asia WGS AF: 0.0500 AC: 176 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Uncertain	0.98
PhyloP100		0.050
PromoterAI		0.33	Neutral

Splicing

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

Other links and lift over

dbSNP: rs28999109; hg19: chr4-157893041;