rs1217389

Positions:

• chr1-113823130-C-T

Variant summary

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

The ENST00000359785.10(PTPN22):​c.2281+2012G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 151,866 control chromosomes in the GnomAD database, including 44,692 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 0.76 (44689 hom., cov: 32)
  • Exomes 𝑓: 0.64 (3 hom.)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN22	NM_015967.8	c.2281+2012G>A		intron_variant		ENST00000359785.10
PTPN22	XM_047417630.1	c.2131+2012G>A		intron_variant
AP4B1-AS1	NR_125965.1	n.414+7658C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.2281+2012G>A		intron_variant		1	NM_015967.8	P1
	ENST00000664434.1	n.418+7658C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115466 AN: 151734 Hom.: 44641 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.643 AC: 9 AN: 14 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 8 AN XY: 12

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.761 AC: 115575 AN: 151852 Hom.: 44689 Cov.: 32 AF XY: 0.754 AC XY: 55999 AN XY: 74224

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.741

Alfa AF: 0.757 Hom.: 45696

Bravo AF: 0.753

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.8
DANN	Benign	0.43

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: rs1217389; hg19: chr1-114365752;