dbSNP rs35448850: PTPN22:c.750+112T>A (chr1-113854359-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000359785.10(PTPN22):c.750+112T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,062,980 control chromosomes in the GnomAD database, including 24 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 0.0028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 24 hom. )

Consequence

PTPN22
ENST00000359785.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

0 publications found

Variant links:

Genes affected

PTPN22 (HGNC:9652): (protein tyrosine phosphatase non-receptor type 22) This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Mar 2009]

PTPN22 links:

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

AP4B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS2

High Homozygotes in GnomAdExome4 at 24 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PTPN22	NM_015967.8 link	c.750+112T>A	intron_variant	Intron 9 of 20	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.2 link	c.678+112T>A	intron_variant	Intron 8 of 19	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.3 link	c.750+112T>A	intron_variant	Intron 9 of 20	NP_001180360.2	Q9Y2R2-4B4DZW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10 link	c.750+112T>A		intron_variant	Intron 9 of 20	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

420

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.00431

GnomAD4 exome

AF:

0.00390

AC:

3556

AN:

910682

Hom.:

AF XY:

0.00425

AC XY:

1977

AN XY:

465290

show subpopulations

African (AFR)

AF:

0.000605

AC:

AN:

21486

American (AMR)

AF:

0.00277

AC:

AN:

32142

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

235

AN:

19900

East Asian (EAS)

AF:

0.00

AC:

AN:

34662

South Asian (SAS)

AF:

0.0103

AC:

658

AN:

64016

European-Finnish (FIN)

AF:

0.000372

AC:

AN:

48430

Middle Eastern (MID)

AF:

0.00374

AC:

AN:

4546

European-Non Finnish (NFE)

AF:

0.00365

AC:

2351

AN:

643522

Other (OTH)

AF:

0.00417

AC:

175

AN:

41978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

180

360

539

719

899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.00275

AC:

419

AN:

152298

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41566

American (AMR)

AF:

0.00333

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00366

AC:

249

AN:

68022

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00291

Hom.:

Bravo

AF:

0.00271

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.6

(source)

DANN

Benign

0.69

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over