4-156962953-A-G

Variant names:

• chr4-156962953-A-G
• rs6845322
• NM_016205.3:c.118+7833T>C

Variant summary

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

The NM_016205.3(PDGFC):​c.118+7833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,970 control chromosomes in the GnomAD database, including 13,662 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 0.41 (13662 hom., cov: 32)
• Consequence: PDGFC NM_016205.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016205.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFC	NM_016205.3	MANE Select	c.118+7833T>C		intron	N/A	NP_057289.1
	PDGFC	NR_036641.2		n.1014+7833T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFC	ENST00000502773.6	TSL:1 MANE Select	c.118+7833T>C		intron	N/A	ENSP00000422464.1
	PDGFC	ENST00000274071.6	TSL:1	n.118+7833T>C		intron	N/A	ENSP00000274071.2
	PDGFC	ENST00000422544.2	TSL:5	c.118+7833T>C		intron	N/A	ENSP00000410048.2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62400 AN: 151852 Hom.: 13627 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.411 AC: 62491 AN: 151970 Hom.: 13662 Cov.: 32 AF XY: 0.416 AC XY: 30936 AN XY: 74298

African (AFR) AF: 0.553 AC: 22904 AN: 41428

American (AMR) AF: 0.435 AC: 6639 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2334 AN: 5140

South Asian (SAS) AF: 0.540 AC: 2605 AN: 4826

European-Finnish (FIN) AF: 0.359 AC: 3796 AN: 10576

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21901 AN: 67952

Other (OTH) AF: 0.375 AC: 791 AN: 2110

Alfa AF: 0.350 Hom.: 43358

Bravo AF: 0.418

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.054
DANN	Benign	0.44
PhyloP100		-1.1
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: rs6845322; hg19: chr4-157884105;