rs322236

Variant names:

• chr7-137270152-A-G
• rs322236
• NM_002825.7:c.-1-15178T>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.-1-15178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,152 control chromosomes in the GnomAD database, including 13,069 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 0.36 (13069 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002825.7. 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
	PTN	NM_002825.7	MANE Select	c.-1-15178T>C		intron	N/A	NP_002816.1
	PTN	NM_001321387.3		c.-1-15178T>C		intron	N/A	NP_001308316.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTN	ENST00000348225.7	TSL:1 MANE Select	c.-1-15178T>C		intron	N/A	ENSP00000341170.2
	PTN	ENST00000699293.1		c.-1-15178T>C		intron	N/A	ENSP00000514273.1
	PTN	ENST00000393083.2	TSL:5	c.-1-15178T>C		intron	N/A	ENSP00000376798.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54574 AN: 152034 Hom.: 13027 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.359 AC: 54663 AN: 152152 Hom.: 13069 Cov.: 32 AF XY: 0.353 AC XY: 26221 AN XY: 74378

African (AFR) AF: 0.690 AC: 28609 AN: 41480

American (AMR) AF: 0.227 AC: 3471 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1136 AN: 3470

East Asian (EAS) AF: 0.0587 AC: 304 AN: 5178

South Asian (SAS) AF: 0.158 AC: 761 AN: 4826

European-Finnish (FIN) AF: 0.237 AC: 2510 AN: 10588

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16958 AN: 68000

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.305 Hom.: 16700

Bravo AF: 0.372

Asia WGS AF: 0.162 AC: 566 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.57
PhyloP100		-0.90
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: rs322236; hg19: chr7-136954899;