rs2476599

Variant names:

• chr1-113820837-G-A
• rs2476599
• ENST00000359785.10:c.2282-1183C>T

Variant summary

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

The ENST00000359785.10(PTPN22):​c.2282-1183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,874 control chromosomes in the GnomAD database, including 10,786 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 0.34 (10786 hom., cov: 32)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64
• Publications: 33 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2282-1183C>T		intron_variant	Intron 19 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.2210-1183C>T		intron_variant	Intron 18 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.2198-1183C>T		intron_variant	Intron 19 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2282-1183C>T		intron_variant	Intron 19 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51881 AN: 151760 Hom.: 10765 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.342 AC: 51944 AN: 151874 Hom.: 10786 Cov.: 32 AF XY: 0.336 AC XY: 24924 AN XY: 74230

African (AFR) AF: 0.578 AC: 23933 AN: 41406

American (AMR) AF: 0.220 AC: 3353 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3470

East Asian (EAS) AF: 0.0684 AC: 354 AN: 5172

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4822

European-Finnish (FIN) AF: 0.239 AC: 2504 AN: 10494

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18486 AN: 67922

Other (OTH) AF: 0.298 AC: 630 AN: 2114

Alfa AF: 0.281 Hom.: 9817

Bravo AF: 0.345

Asia WGS AF: 0.194 AC: 675 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.69
PhyloP100		-3.6
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: rs2476599; hg19: chr1-114363459;