dbSNP rs7895103: PTPRE:c.-8+16398T>C (chr10-127998694-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006504.6(PTPRE):c.-8+16398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,082 control chromosomes in the GnomAD database, including 4,534 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 0.24 ( 4534 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTPRE
NM_006504.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.99

Publications

10 publications found

Variant links:

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]

PTPRE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRE	NM_006504.6 link	c.-8+16398T>C		intron_variant	Intron 2 of 20	ENST00000254667.8	NP_006495.1	P23469-1Q96P81

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPRE	ENST00000254667.8 link	c.-8+16398T>C	intron_variant	Intron 2 of 20	1	NM_006504.6	ENSP00000254667.3	P23469-1
PTPRE	ENST00000455661.5 link	c.-1275T>C	5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000416939.1	Q5VWH5
PTPRE	ENST00000471218.5 link	c.-8+11299T>C	intron_variant	Intron 1 of 5	3		ENSP00000474102.1	S4R3B0
PTPRE	ENST00000442830.5 link	c.-8+16398T>C	intron_variant	Intron 3 of 6	5		ENSP00000410540.1	Q5VWH6

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36747

AN:

151962

Hom.:

4537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.411

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.240

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.242

AC:

36763

AN:

152082

Hom.:

4534

Cov.:

AF XY:

0.239

AC XY:

17798

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.225

AC:

9334

AN:

41478

American (AMR)

AF:

0.239

AC:

3651

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1055

AN:

3468

East Asian (EAS)

AF:

0.175

AC:

906

AN:

5178

South Asian (SAS)

AF:

0.305

AC:

1471

AN:

4818

European-Finnish (FIN)

AF:

0.191

AC:

2016

AN:

10572

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17372

AN:

67990

Other (OTH)

AF:

0.241

AC:

507

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1441

2883

4324

5766

7207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

3037

Bravo

AF:

0.243

Asia WGS

AF:

0.238

AC:

831

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.053

(source)

DANN

Benign

0.70

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over