rs7081735

Positions:

• chr10-127998792-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+16496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,994 control chromosomes in the GnomAD database, including 39,171 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 0.71 (39169 hom., cov: 31)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRE	NM_006504.6	c.-8+16496G>A		intron_variant		ENST00000254667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRE	ENST00000254667.8	c.-8+16496G>A		intron_variant		1	NM_006504.6
PTPRE	ENST00000455661.5	c.-1177G>A		5_prime_UTR_variant	1/6	2
PTPRE	ENST00000442830.5	c.-8+16496G>A		intron_variant		5
PTPRE	ENST00000471218.5	c.-8+11397G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108154 AN: 151870 Hom.: 39124 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.656

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.712 AC: 108248 AN: 151988 Hom.: 39169 Cov.: 31 AF XY: 0.713 AC XY: 53007 AN XY: 74294

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.655

Alfa AF: 0.696 Hom.: 8953

Bravo AF: 0.713

Asia WGS AF: 0.658 AC: 2289 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	0.14
DANN	Benign	0.62

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: rs7081735; hg19: chr10-129797056;