7-137281117-G-T

Variant names:

• chr7-137281117-G-T
• rs1880791
• NM_002825.7:c.-1-26143C>A

Variant summary

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

The ENST00000348225.7(PTN):​c.-1-26143C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,980 control chromosomes in the GnomAD database, including 1,587 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 0.13 (1587 hom., cov: 30)
• Consequence: PTN ENST00000348225.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000348225.7. 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.-1-26143C>A		intron	N/A	NP_002816.1
	PTN	NM_001321387.3		c.-1-26143C>A		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.-1-26143C>A		intron	N/A	ENSP00000341170.2
	PTN	ENST00000699293.1		c.-1-26143C>A		intron	N/A	ENSP00000514273.1
	PTN	ENST00000393083.2	TSL:5	c.-1-26143C>A		intron	N/A	ENSP00000376798.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19558 AN: 151864 Hom.: 1585 Cov.: 30

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.129 AC: 19564 AN: 151980 Hom.: 1587 Cov.: 30 AF XY: 0.129 AC XY: 9607 AN XY: 74282

African (AFR) AF: 0.0335 AC: 1389 AN: 41480

American (AMR) AF: 0.137 AC: 2089 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3466

East Asian (EAS) AF: 0.175 AC: 903 AN: 5154

South Asian (SAS) AF: 0.198 AC: 953 AN: 4816

European-Finnish (FIN) AF: 0.147 AC: 1542 AN: 10522

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11747 AN: 67960

Other (OTH) AF: 0.133 AC: 281 AN: 2110

Alfa AF: 0.162 Hom.: 1302

Bravo AF: 0.123

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		0.24
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: rs1880791; hg19: chr7-136965864;