4-156895991-A-G

Variant names:

• chr4-156895991-A-G
• rs894588
• NM_016205.3:c.119-45575T>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.119-45575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,788 control chromosomes in the GnomAD database, including 26,685 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 0.59 (26685 hom., cov: 31)
• Consequence: PDGFC NM_016205.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.632 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.119-45575T>C		intron	N/A	NP_057289.1
	PDGFC	NR_036641.2		n.1015-34502T>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.119-45575T>C		intron	N/A	ENSP00000422464.1
	PDGFC	ENST00000274071.6	TSL:1	n.119-34502T>C		intron	N/A	ENSP00000274071.2
	PDGFC	ENST00000422544.2	TSL:5	c.119-45575T>C		intron	N/A	ENSP00000410048.2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89667 AN: 151666 Hom.: 26666 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.591 AC: 89740 AN: 151788 Hom.: 26685 Cov.: 31 AF XY: 0.592 AC XY: 43883 AN XY: 74124

African (AFR) AF: 0.596 AC: 24650 AN: 41378

American (AMR) AF: 0.642 AC: 9802 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3234 AN: 5138

South Asian (SAS) AF: 0.357 AC: 1722 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6826 AN: 10494

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.590 AC: 40060 AN: 67918

Other (OTH) AF: 0.590 AC: 1244 AN: 2110

Alfa AF: 0.589 Hom.: 3387

Bravo AF: 0.593

Asia WGS AF: 0.497 AC: 1722 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.74
PhyloP100		-0.17
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: rs894588; hg19: chr4-157817143;