4-156812838-G-T

Variant names:

• chr4-156812838-G-T
• rs10517653
• NM_016205.3:c.315-1821C>A

Variant summary

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

The NM_016205.3(PDGFC):​c.315-1821C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,030 control chromosomes in the GnomAD database, including 1,552 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 0.14 (1552 hom., cov: 32)
• Consequence: PDGFC NM_016205.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.315-1821C>A		intron_variant	Intron 2 of 5	ENST00000502773.6	NP_057289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773.6	c.315-1821C>A		intron_variant	Intron 2 of 5	1	NM_016205.3	ENSP00000422464.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21426 AN: 151912 Hom.: 1553 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.141 AC: 21420 AN: 152030 Hom.: 1552 Cov.: 32 AF XY: 0.141 AC XY: 10491 AN XY: 74316

African (AFR) AF: 0.124 AC: 5126 AN: 41504

American (AMR) AF: 0.148 AC: 2259 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 463 AN: 3468

East Asian (EAS) AF: 0.0465 AC: 241 AN: 5178

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4818

European-Finnish (FIN) AF: 0.152 AC: 1610 AN: 10566

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10234 AN: 67948

Other (OTH) AF: 0.137 AC: 288 AN: 2104

Alfa AF: 0.147 Hom.: 1932

Bravo AF: 0.137

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10517653; hg19: chr4-157733990;