rs322302

chr7-137246805-C-T

Variant summary

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

The NM_002825.7(PTN):c.451+4425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 152,160 control chromosomes in the GnomAD database, including 779 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 0.098 (779 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

Genes affected

PTN (HGNC:9630): (pleiotrophin) The protein encoded by this gene is a secreted heparin-binding growth factor. The protein has significant roles in cell growth and survival, cell migration, angiogenesis and tumorigenesis. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTN	NM_002825.7	c.451+4425G>A		intron_variant		ENST00000348225.7
PTN	NM_001321386.2	c.451+4425G>A		intron_variant
PTN	NM_001321387.3	c.451+4425G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTN	ENST00000348225.7	c.451+4425G>A		intron_variant		1	NM_002825.7	P1
PTN	ENST00000393083.2	c.451+4425G>A		intron_variant		5
PTN	ENST00000699293.1	c.451+4425G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14886 AN: 152042 Hom.: 780 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.0979 AC: 14891 AN: 152160 Hom.: 779 Cov.: 32 AF XY: 0.0951 AC XY: 7075 AN XY: 74402

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0921

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0904

Alfa AF: 0.105 Hom.: 861

Bravo AF: 0.100

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.13
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs322302; hg19: chr7-136931552;