rs4369314

chr10-127994794-G-A

Variant summary

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

The NM_006504.6(PTPRE):c.-8+12498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,066 control chromosomes in the GnomAD database, including 3,798 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 0.22 (3798 hom., cov: 32)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

Genes affected

PTPRE (HGNC:9669): (protein tyrosine phosphatase receptor type E) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Several alternatively spliced transcript variants of this gene have been reported, at least two of which encode a receptor-type PTP that possesses a short extracellular domain, a single transmembrane region, and two tandem intracytoplasmic catalytic domains; another one encodes a PTP that contains a distinct hydrophilic N-terminus, and thus represents a nonreceptor-type isoform of this PTP. Studies of the similar gene in mice suggested the regulatory roles of this PTP in RAS related signal transduction pathways, cytokine-induced SATA signaling, as well as the activation of voltage-gated K+ channels. [provided by RefSeq, Oct 2015]

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 (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRE	NM_006504.6	c.-8+12498G>A		intron_variant		ENST00000254667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRE	ENST00000254667.8	c.-8+12498G>A		intron_variant		1	NM_006504.6
PTPRE	ENST00000442830.5	c.-8+12498G>A		intron_variant		5
PTPRE	ENST00000471218.5	c.-8+7399G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33815 AN: 151948 Hom.: 3801 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.222 AC: 33828 AN: 152066 Hom.: 3798 Cov.: 32 AF XY: 0.220 AC XY: 16347 AN XY: 74330

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.224

Alfa AF: 0.226 Hom.: 912

Bravo AF: 0.227

Asia WGS AF: 0.191 AC: 663 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	4.1
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: rs4369314; hg19: chr10-129793058;