rs322323

chr7-137255813-T-C

Variant summary

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

The NM_002825.7(PTN):c.-1-839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,018 control chromosomes in the GnomAD database, including 15,018 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 0.44 (15018 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTN	NM_002825.7	c.-1-839A>G		intron_variant		ENST00000348225.7
PTN	NM_001321386.2	c.-1-839A>G		intron_variant
PTN	NM_001321387.3	c.-1-839A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTN	ENST00000348225.7	c.-1-839A>G		intron_variant		1	NM_002825.7	P1
PTN	ENST00000393083.2	c.-1-839A>G		intron_variant		5
PTN	ENST00000699293.1	c.-1-839A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66893 AN: 151902 Hom.: 14984 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.440 AC: 66961 AN: 152018 Hom.: 15018 Cov.: 32 AF XY: 0.440 AC XY: 32704 AN XY: 74314

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.428

Alfa AF: 0.423 Hom.: 9177

Bravo AF: 0.441

Asia WGS AF: 0.399 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.1
Dann	Benign	0.66

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: rs322323; hg19: chr7-136940560;