rs322239

Variant names:

• chr7-137271860-C-A
• rs322239
• NM_002825.7:c.-1-16886G>T

Variant summary

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

The NM_002825.7(PTN):​c.-1-16886G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,254 control chromosomes in the GnomAD database, including 57,396 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 0.87 (57396 hom., cov: 33)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTN	NM_002825.7	c.-1-16886G>T		intron_variant	Intron 1 of 4	ENST00000348225.7	NP_002816.1
PTN	NM_001321387.3	c.-1-16886G>T		intron_variant	Intron 1 of 4		NP_001308316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTN	ENST00000348225.7	c.-1-16886G>T		intron_variant	Intron 1 of 4	1	NM_002825.7	ENSP00000341170.2
PTN	ENST00000699293.1	c.-1-16886G>T		intron_variant	Intron 1 of 4			ENSP00000514273.1
PTN	ENST00000393083.2	c.-1-16886G>T		intron_variant	Intron 1 of 5	5		ENSP00000376798.2

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131750 AN: 152136 Hom.: 57365 Cov.: 33

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.866 AC: 131838 AN: 152254 Hom.: 57396 Cov.: 33 AF XY: 0.871 AC XY: 64828 AN XY: 74450

African (AFR) AF: 0.771 AC: 32017 AN: 41528

American (AMR) AF: 0.901 AC: 13780 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2951 AN: 3468

East Asian (EAS) AF: 0.989 AC: 5123 AN: 5180

South Asian (SAS) AF: 0.945 AC: 4565 AN: 4830

European-Finnish (FIN) AF: 0.927 AC: 9830 AN: 10606

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60610 AN: 68030

Other (OTH) AF: 0.875 AC: 1850 AN: 2114

Alfa AF: 0.881 Hom.: 100040

Bravo AF: 0.860

Asia WGS AF: 0.956 AC: 3322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.38
PhyloP100		-0.34
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: rs322239; hg19: chr7-136956607;