Variant chr1-113858609-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000359785.10(PTPN22):c.274-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,284,472 control chromosomes in the GnomAD database, including 205,272 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 0.56 ( 24715 hom., cov: 27)

Exomes 𝑓: 0.56 ( 180557 hom. )

Consequence

PTPN22
ENST00000359785.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.104

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PTPN22	NM_015967.8 linkuse as main transcript	c.274-36T>C	intron_variant	ENST00000359785.10	NP_057051.4
PTPN22	XM_047417630.1 linkuse as main transcript	c.274-36T>C	intron_variant		XP_047273586.1
AP4B1-AS1	NR_125965.1 linkuse as main transcript	n.415-39259A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
PTPN22	ENST00000359785.10 linkuse as main transcript	c.274-36T>C	intron_variant	1	NM_015967.8	ENSP00000352833	P1
AP4B1-AS1	ENST00000419536.1 linkuse as main transcript	n.246+593A>G	intron_variant, non_coding_transcript_variant	2
	ENST00000664434.1 linkuse as main transcript	n.504+593A>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85010

AN:

151234

Hom.:

24688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.548

GnomAD3 exomes

AF:

0.531

AC:

78253

AN:

147410

Hom.:

21973

AF XY:

0.539

AC XY:

42187

AN XY:

78212

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.672

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.557

AC:

630651

AN:

1133126

Hom.:

180557

Cov.:

AF XY:

0.560

AC XY:

319173

AN XY:

569658

show subpopulations

Gnomad4 AFR exome

AF:

0.655

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.594

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.661

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.559

GnomAD4 genome

AF:

0.562

AC:

85084

AN:

151346

Hom.:

24715

Cov.:

AF XY:

0.556

AC XY:

41154

AN XY:

73956

show subpopulations

Gnomad4 AFR

AF:

0.648

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.606

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.652

Gnomad4 FIN

AF:

0.487

Gnomad4 NFE

AF:

0.568

Gnomad4 OTH

AF:

0.544

Alfa

AF:

0.566

Hom.:

13422

Bravo

AF:

0.555

Asia WGS

AF:

0.438

AC:

1524

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

0.70

DANN

Benign

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over