dbSNP rs11582409: PTPN22:c.409-192G>A (chr1-113856811-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 NM_015967.8(PTPN22):c.409-192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 649,238 control chromosomes in the GnomAD database, including 9,925 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 0.16 ( 2110 hom., cov: 32)

Exomes 𝑓: 0.17 ( 7815 hom. )

Consequence

PTPN22
NM_015967.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.700

Publications

13 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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8 link	c.409-192G>A		intron_variant	Intron 5 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10 link	c.409-192G>A		intron_variant	Intron 5 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23750

AN:

152054

Hom.:

2109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0818

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.161

GnomAD4 exome

AF:

0.172

AC:

85557

AN:

497066

Hom.:

7815

Cov.:

AF XY:

0.169

AC XY:

43381

AN XY:

256248

show subpopulations

African (AFR)

AF:

0.0778

AC:

1047

AN:

13466

American (AMR)

AF:

0.145

AC:

2272

AN:

15674

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

1982

AN:

13132

East Asian (EAS)

AF:

0.208

AC:

6123

AN:

29454

South Asian (SAS)

AF:

0.106

AC:

4125

AN:

38806

European-Finnish (FIN)

AF:

0.180

AC:

5278

AN:

29286

Middle Eastern (MID)

AF:

0.122

AC:

335

AN:

2750

European-Non Finnish (NFE)

AF:

0.183

AC:

59899

AN:

328038

Other (OTH)

AF:

0.170

AC:

4496

AN:

26460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3323

6646

9968

13291

16614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

996

1992

2988

3984

4980

<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:

0.156

AC:

23760

AN:

152172

Hom.:

2110

Cov.:

AF XY:

0.157

AC XY:

11677

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0819

AC:

3401

AN:

41546

American (AMR)

AF:

0.170

AC:

2593

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

545

AN:

3466

East Asian (EAS)

AF:

0.230

AC:

1189

AN:

5176

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4822

European-Finnish (FIN)

AF:

0.197

AC:

2081

AN:

10554

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12789

AN:

68002

Other (OTH)

AF:

0.165

AC:

349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1045

2091

3136

4182

5227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.153

Hom.:

408

Bravo

AF:

0.153

Asia WGS

AF:

0.195

AC:

680

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.1

(source)

DANN

Benign

0.50

PhyloP100

-0.70

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