rs2476599

Positions:

• chr1-113820837-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015967.8(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 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64

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]

ENSG00000231128 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2282-1183C>T		intron_variant			NP_057051.4
PTPN22	NM_001308297.2	c.2210-1183C>T		intron_variant			NP_001295226.2
PTPN22	NM_001193431.3	c.2198-1183C>T		intron_variant			NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2282-1183C>T		intron_variant		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

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.0684

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.298

Alfa AF: 0.277 Hom.: 8030

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

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

Other links and lift over

dbSNP: rs2476599; hg19: chr1-114363459;