rs7081735

Variant names:

• chr10-127998792-G-A
• rs7081735
• NM_006504.6:c.-8+16496G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254667.8(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 ENST00000254667.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000254667.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	NM_006504.6	MANE Select	c.-8+16496G>A		intron	N/A	NP_006495.1
	PTPRE	NM_001323354.2		c.-1177G>A		5_prime_UTR	Exon 1 of 20	NP_001310283.1
	PTPRE	NM_001323355.2		c.54-42083G>A		intron	N/A	NP_001310284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	ENST00000254667.8	TSL:1 MANE Select	c.-8+16496G>A		intron	N/A	ENSP00000254667.3
	PTPRE	ENST00000455661.5	TSL:2	c.-1177G>A		5_prime_UTR	Exon 1 of 6	ENSP00000416939.1
	PTPRE	ENST00000471218.5	TSL:3	c.-8+11397G>A		intron	N/A	ENSP00000474102.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.855 AC: 35456 AN: 41446

American (AMR) AF: 0.632 AC: 9645 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2256 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3142 AN: 5160

South Asian (SAS) AF: 0.752 AC: 3618 AN: 4808

European-Finnish (FIN) AF: 0.691 AC: 7283 AN: 10540

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44545 AN: 67992

Other (OTH) AF: 0.655 AC: 1380 AN: 2106

Alfa AF: 0.689 Hom.: 14953

Bravo AF: 0.713

Asia WGS AF: 0.658 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.62
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7081735; hg19: chr10-129797056;