7-137250712-T-G

Variant names:

• chr7-137250712-T-G
• rs322297
• NM_002825.7:c.451+518A>C

Variant summary

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

The NM_002825.7(PTN):​c.451+518A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,188 control chromosomes in the GnomAD database, including 1,613 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 (1613 hom., cov: 33)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTN	NM_002825.7	c.451+518A>C		intron_variant	Intron 4 of 4	ENST00000348225.7	NP_002816.1
PTN	NM_001321386.2	c.451+518A>C		intron_variant	Intron 4 of 4		NP_001308315.1
PTN	NM_001321387.3	c.451+518A>C		intron_variant	Intron 4 of 4		NP_001308316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTN	ENST00000348225.7	c.451+518A>C		intron_variant	Intron 4 of 4	1	NM_002825.7	ENSP00000341170.2
PTN	ENST00000699293.1	c.451+518A>C		intron_variant	Intron 4 of 4			ENSP00000514273.1
PTN	ENST00000393083.2	c.451+518A>C		intron_variant	Intron 4 of 5	5		ENSP00000376798.2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21002 AN: 152070 Hom.: 1612 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.138 AC: 21016 AN: 152188 Hom.: 1613 Cov.: 33 AF XY: 0.135 AC XY: 10050 AN XY: 74412

African (AFR) AF: 0.201 AC: 8323 AN: 41508

American (AMR) AF: 0.112 AC: 1710 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 581 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.100 AC: 483 AN: 4824

European-Finnish (FIN) AF: 0.0765 AC: 810 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.128 AC: 8701 AN: 67994

Other (OTH) AF: 0.127 AC: 268 AN: 2114

Alfa AF: 0.131 Hom.: 1852

Bravo AF: 0.144

Asia WGS AF: 0.0720 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.78
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs322297; hg19: chr7-136935459;