rs322236

Positions:

• chr7-137270152-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTN	NM_002825.7	c.-1-15178T>C		intron_variant		ENST00000348225.7	NP_002816.1
PTN	NM_001321387.3	c.-1-15178T>C		intron_variant			NP_001308316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTN	ENST00000348225.7	c.-1-15178T>C		intron_variant		1	NM_002825.7	ENSP00000341170.2
PTN	ENST00000699293.1	c.-1-15178T>C		intron_variant				ENSP00000514273.1
PTN	ENST00000393083.2	c.-1-15178T>C		intron_variant		5		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

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.321

Alfa AF: 0.266 Hom.: 7900

Bravo AF: 0.372

Asia WGS AF: 0.162 AC: 566 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.57

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: rs322236; hg19: chr7-136954899;