Genetic Variant PTPRB:c.4994-159A>G (chr12-70555468-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_001109754.4(PTPRB):c.4994-159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,982 control chromosomes in the GnomAD database, including 11,856 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 0.38 ( 11856 hom., cov: 32)

Consequence

PTPRB
NM_001109754.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

Publications

6 publications found

Variant links:

Genes affected

PTPRB (HGNC:9665): (protein tyrosine phosphatase receptor type B) 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. This PTP contains an extracellular domain, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to receptor type PTP. The extracellular region of this PTP is composed of multiple fibronectin type_III repeats, which was shown to interact with neuronal receptor and cell adhesion molecules, such as contactin and tenascin C. This protein was also found to interact with sodium channels, and thus may regulate sodium channels by altering tyrosine phosphorylation status. The functions of the interaction partners of this protein implicate the roles of this PTP in cell adhesion, neurite growth, and neuronal differentiation. Alternate transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

PTPRB links:

ENSG00000299164 (HGNC:):

ENSG00000299164 links:

PTPRB-AS1 (HGNC:58150):

PTPRB-AS1 links:

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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=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRB	NM_001109754.4 link	c.4994-159A>G		intron_variant	Intron 19 of 33	ENST00000334414.11	NP_001103224.1	P23467-3Q86VA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11 link	c.4994-159A>G		intron_variant	Intron 19 of 33	1	NM_001109754.4	ENSP00000334928.6		P23467-3

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57520

AN:

151868

Hom.:

11846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.432

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

GnomAD4 genome

AF:

0.379

AC:

57555

AN:

151982

Hom.:

11856

Cov.:

AF XY:

0.382

AC XY:

28382

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.207

AC:

8599

AN:

41472

American (AMR)

AF:

0.431

AC:

6574

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1607

AN:

3468

East Asian (EAS)

AF:

0.542

AC:

2781

AN:

5128

South Asian (SAS)

AF:

0.401

AC:

1927

AN:

4810

European-Finnish (FIN)

AF:

0.437

AC:

4615

AN:

10558

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.440

AC:

29887

AN:

67964

Other (OTH)

AF:

0.433

AC:

913

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1741

3481

5222

6962

8703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.430

Hom.:

28093

Bravo

AF:

0.372

Asia WGS

AF:

0.460

AC:

1602

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.5

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

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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