rs11056571

chr12-15577486-G-A

Variant summary

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

The NM_030667.3(PTPRO):c.2830-1367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,130 control chromosomes in the GnomAD database, including 2,886 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 0.19 (2886 hom., cov: 33)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386

Genes affected

PTPRO (HGNC:9678): (protein tyrosine phosphatase receptor type O) This gene encodes a member of the R3 subtype family of receptor-type protein tyrosine phosphatases. These proteins are localized to the apical surface of polarized cells and may have tissue-specific functions through activation of Src family kinases. This gene contains two distinct promoters, and alternatively spliced transcript variants encoding multiple isoforms have been observed. The encoded proteins may have multiple isoform-specific and tissue-specific functions, including the regulation of osteoclast production and activity, inhibition of cell proliferation and facilitation of apoptosis. This gene is a candidate tumor suppressor, and decreased expression of this gene has been observed in several types of cancer. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRO	NM_030667.3	c.2830-1367G>A		intron_variant		ENST00000281171.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRO	ENST00000281171.9	c.2830-1367G>A		intron_variant		1	NM_030667.3	P4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28846 AN: 152012 Hom.: 2890 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.190 AC: 28857 AN: 152130 Hom.: 2886 Cov.: 33 AF XY: 0.192 AC XY: 14246 AN XY: 74346

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.222

Alfa AF: 0.180 Hom.: 508

Bravo AF: 0.190

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.9
Dann	Benign	0.49

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: rs11056571; hg19: chr12-15730420;