Genetic Variant PTPN22:c.1895-166G>T (chr1-113834605-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000359785.10(PTPN22):c.1895-166G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 152,260 control chromosomes in the GnomAD database, including 48 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 0.021 ( 48 hom., cov: 32)

Consequence

PTPN22
ENST00000359785.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

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:

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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=-0.83).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0207 (3147/152260) while in subpopulation NFE AF = 0.0297 (2019/68026). AF 95% confidence interval is 0.0286. There are 48 homozygotes in GnomAd4. There are 1478 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 48 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PTPN22	NM_015967.8 link	c.1895-166G>T	intron_variant	Intron 14 of 20	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.2 link	c.1823-166G>T	intron_variant	Intron 13 of 19	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.3 link	c.1895-166G>T	intron_variant	Intron 14 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.1895-166G>T		intron_variant	Intron 14 of 20	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3145

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00656

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0297

Gnomad OTH

AF:

0.0191

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

GnomAD4 genome

AF:

0.0207

AC:

3147

AN:

152260

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1478

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00655

AC:

272

AN:

41556

American (AMR)

AF:

0.0153

AC:

234

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3472

East Asian (EAS)

AF:

0.0158

AC:

AN:

5188

South Asian (SAS)

AF:

0.0243

AC:

117

AN:

4822

European-Finnish (FIN)

AF:

0.0246

AC:

260

AN:

10590

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0297

AC:

2019

AN:

68026

Other (OTH)

AF:

0.0189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

148

296

445

593

741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0242

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(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