rs3733486

Positions:

• chr4-156971282-G-A

Variant summary

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

The NM_016205.3(PDGFC):​c.-379C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00952 in 424,826 control chromosomes in the GnomAD database, including 250 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 0.0043 (21 hom., cov: 31)
  • Exomes 𝑓: 0.012 (229 hom.)
• Consequence: PDGFC NM_016205.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFC	NM_016205.3	c.-379C>T		5_prime_UTR_variant	1/6	ENST00000502773.6
PDGFC	NR_036641.2	n.518C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFC	ENST00000502773.6	c.-379C>T		5_prime_UTR_variant	1/6	1	NM_016205.3	P1
PDGFC	ENST00000274071.6	c.-379C>T		5_prime_UTR_variant, NMD_transcript_variant	1/7	1

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 656 AN: 151930 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000648

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.0124 AC: 3392 AN: 272786 Hom.: 229 Cov.: 0 AF XY: 0.0120 AC XY: 1665 AN XY: 138656

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.000203

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.00689

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000759

Gnomad4 OTH exome AF: 0.00637

GnomAD4 genome AF: 0.00429 AC: 652 AN: 152040 Hom.: 21 Cov.: 31 AF XY: 0.00464 AC XY: 345 AN XY: 74292

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0985

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000648

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00167 Hom.: 3

Bravo AF: 0.00457

Asia WGS AF: 0.0470 AC: 164 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3733486; hg19: chr4-157892434;