rs4764191

Positions:

• chr12-15407262-A-G
• chr12-15407262-A-T

Variant summary

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

The NM_030667.3(PTPRO):​c.76-76712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,180 control chromosomes in the GnomAD database, including 56,085 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 0.85 (56085 hom., cov: 32)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRO	NM_030667.3	c.76-76712A>G		intron_variant		ENST00000281171.9	NP_109592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRO	ENST00000281171.9	c.76-76712A>G		intron_variant		1	NM_030667.3	ENSP00000281171	P4

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128846 AN: 152062 Hom.: 56068 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.847 AC: 128907 AN: 152180 Hom.: 56085 Cov.: 32 AF XY: 0.852 AC XY: 63379 AN XY: 74420

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.880

Alfa AF: 0.918 Hom.: 84658

Bravo AF: 0.834

Asia WGS AF: 0.919 AC: 3196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.82

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: rs4764191; hg19: chr12-15560196;