Genetic Variant PTPRB:p.Ala1473Ala (chr12-70560684-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001109754.4(PTPRB):c.4419G>A(p.Ala1473Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 1,612,790 control chromosomes in the GnomAD database, including 524 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 0.033 ( 235 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 289 hom. )

Consequence

PTPRB
NM_001109754.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=-1.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRB	NM_001109754.4 link	c.4419G>A	p.Ala1473Ala	synonymous_variant	Exon 17 of 34	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.4419G>A	p.Ala1473Ala	synonymous_variant	Exon 17 of 34	1	NM_001109754.4	ENSP00000334928.6		P23467-3

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5052

AN:

151064

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.0194

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.0314

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00294

Gnomad OTH

AF:

0.0319

GnomAD2 exomes

AF:

0.0139

AC:

3453

AN:

249034

AF XY:

0.0135

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.00722

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.00304

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.00694

AC:

10138

AN:

1461608

Hom.:

289

Cov.:

AF XY:

0.00737

AC XY:

5360

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.109

AC:

3654

AN:

33478

American (AMR)

AF:

0.00763

AC:

341

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0165

AC:

432

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0296

AC:

2550

AN:

86238

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.0384

AC:

220

AN:

5724

European-Non Finnish (NFE)

AF:

0.00190

AC:

2116

AN:

1111850

Other (OTH)

AF:

0.0135

AC:

812

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

560

1119

1679

2238

2798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0334

AC:

5054

AN:

151182

Hom.:

235

Cov.:

AF XY:

0.0326

AC XY:

2410

AN XY:

73890

show subpopulations

African (AFR)

AF:

0.106

AC:

4358

AN:

41116

American (AMR)

AF:

0.0136

AC:

206

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.0194

AC:

AN:

3454

East Asian (EAS)

AF:

0.000197

AC:

AN:

5084

South Asian (SAS)

AF:

0.0315

AC:

149

AN:

4736

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00294

AC:

199

AN:

67732

Other (OTH)

AF:

0.0315

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

220

439

659

878

1098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0128

Hom.:

133

Bravo

AF:

0.0368

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.4

(source)

DANN

Benign

0.50

PhyloP100

-1.8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over