dbSNP rs3789609: PTPN22:c.541-128G>A (chr1-113855177-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000359785.10(PTPN22):c.541-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 757,308 control chromosomes in the GnomAD database, including 29,972 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 0.22 ( 4521 hom., cov: 31)

Exomes 𝑓: 0.28 ( 25451 hom. )

Consequence

PTPN22
ENST00000359785.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.62

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PTPN22	NM_015967.8 link	c.541-128G>A	intron_variant	Intron 7 of 20	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.2 link	c.469-128G>A	intron_variant	Intron 6 of 19	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.3 link	c.541-128G>A	intron_variant	Intron 7 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.541-128G>A		intron_variant	Intron 7 of 20	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33062

AN:

152012

Hom.:

4522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.0936

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.247

GnomAD4 exome

AF:

0.280

AC:

169432

AN:

605178

Hom.:

25451

AF XY:

0.286

AC XY:

89724

AN XY:

313996

show subpopulations

African (AFR)

AF:

0.0544

AC:

837

AN:

15376

American (AMR)

AF:

0.239

AC:

5239

AN:

21952

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

4261

AN:

14974

East Asian (EAS)

AF:

0.0861

AC:

2760

AN:

32068

South Asian (SAS)

AF:

0.380

AC:

18499

AN:

48706

European-Finnish (FIN)

AF:

0.250

AC:

9258

AN:

36986

Middle Eastern (MID)

AF:

0.315

AC:

780

AN:

2476

European-Non Finnish (NFE)

AF:

0.297

AC:

119211

AN:

401532

Other (OTH)

AF:

0.276

AC:

8587

AN:

31108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5750

11500

17251

23001

28751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2058

4116

6174

8232

10290

<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:

0.217

AC:

33068

AN:

152130

Hom.:

4521

Cov.:

AF XY:

0.218

AC XY:

16205

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0593

AC:

2460

AN:

41508

American (AMR)

AF:

0.231

AC:

3528

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1032

AN:

3472

East Asian (EAS)

AF:

0.0936

AC:

485

AN:

5182

South Asian (SAS)

AF:

0.390

AC:

1881

AN:

4818

European-Finnish (FIN)

AF:

0.249

AC:

2637

AN:

10588

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20162

AN:

67978

Other (OTH)

AF:

0.246

AC:

520

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1282

2564

3846

5128

6410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.241

Hom.:

905

Bravo

AF:

0.207

Asia WGS

AF:

0.239

AC:

833

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.87

(source)

DANN

Benign

0.48

PhyloP100

-1.6

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over