rs1880791

Positions:

• chr7-137281117-G-T

Variant summary

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

The NM_002825.7(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 NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTN	NM_002825.7	c.-1-26143C>A		intron_variant		ENST00000348225.7	NP_002816.1
PTN	NM_001321387.3	c.-1-26143C>A		intron_variant			NP_001308316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTN	ENST00000348225.7	c.-1-26143C>A		intron_variant		1	NM_002825.7	ENSP00000341170	P1
PTN	ENST00000393083.2	c.-1-26143C>A		intron_variant		5		ENSP00000376798
PTN	ENST00000699293.1	c.-1-26143C>A		intron_variant				ENSP00000514273

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

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.133

Alfa AF: 0.162 Hom.: 1185

Bravo AF: 0.123

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.70

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: rs1880791; hg19: chr7-136965864;