Genetic Variant ENST00000359785.10:c.2134+47T>C (chr1-113829902-A-G) – 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.2134+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,493,702 control chromosomes in the GnomAD database, including 439 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 0.017 ( 33 hom., cov: 32)

Exomes 𝑓: 0.022 ( 406 hom. )

Consequence

PTPN22
ENST00000359785.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.174

Publications

6 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 = 0.017 (2581/152070) while in subpopulation NFE AF = 0.0257 (1746/67960). AF 95% confidence interval is 0.0247. There are 33 homozygotes in GnomAd4. There are 1204 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PTPN22	NM_015967.8 link	c.2134+47T>C	intron_variant	Intron 17 of 20	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.2 link	c.2062+47T>C	intron_variant	Intron 16 of 19	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.3 link	c.2050+47T>C	intron_variant	Intron 17 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.2134+47T>C		intron_variant	Intron 17 of 20	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2583

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.0162

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0226

GnomAD2 exomes

AF:

0.0184

AC:

4496

AN:

244244

AF XY:

0.0192

show subpopulations

Gnomad AFR exome

AF:

0.00470

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0161

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0228

Gnomad NFE exome

AF:

0.0237

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0224

AC:

30055

AN:

1341632

Hom.:

406

Cov.:

AF XY:

0.0221

AC XY:

14890

AN XY:

673032

show subpopulations

African (AFR)

AF:

0.00383

AC:

117

AN:

30582

American (AMR)

AF:

0.0153

AC:

676

AN:

44104

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

416

AN:

25396

East Asian (EAS)

AF:

0.0000771

AC:

AN:

38912

South Asian (SAS)

AF:

0.0170

AC:

1412

AN:

83116

European-Finnish (FIN)

AF:

0.0199

AC:

1061

AN:

53250

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.0251

AC:

25232

AN:

1004384

Other (OTH)

AF:

0.0189

AC:

1066

AN:

56352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1466

2932

4397

5863

7329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.0170

AC:

2581

AN:

152070

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1204

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00487

AC:

202

AN:

41476

American (AMR)

AF:

0.0162

AC:

248

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0122

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0202

AC:

214

AN:

10588

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0257

AC:

1746

AN:

67960

Other (OTH)

AF:

0.0223

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

129

258

388

517

646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0213

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.00549

AC:

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

(source)

DANN

Benign

0.63

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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