rs3765598

Variant names:

• chr1-113851841-C-T
• rs3765598
• ENST00000359785.10:c.828+186G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359785.10(PTPN22):​c.828+186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,942 control chromosomes in the GnomAD database, including 2,079 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 (2079 hom., cov: 32)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 36 publications found

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]

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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	c.828+186G>A		intron_variant	Intron 10 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.756+186G>A		intron_variant	Intron 9 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.828+186G>A		intron_variant	Intron 10 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.828+186G>A		intron_variant	Intron 10 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23610 AN: 151824 Hom.: 2078 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.155 AC: 23620 AN: 151942 Hom.: 2079 Cov.: 32 AF XY: 0.157 AC XY: 11651 AN XY: 74270

African (AFR) AF: 0.0816 AC: 3377 AN: 41408

American (AMR) AF: 0.170 AC: 2592 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3466

East Asian (EAS) AF: 0.230 AC: 1189 AN: 5170

South Asian (SAS) AF: 0.118 AC: 570 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2100 AN: 10552

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12670 AN: 67942

Other (OTH) AF: 0.164 AC: 346 AN: 2104

Alfa AF: 0.173 Hom.: 3464

Bravo AF: 0.152

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.88
DANN	Benign	0.68
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3765598; hg19: chr1-114394463; COSMIC: COSV63084562; COSMIC: COSV63084562;