rs3789608

Positions:

• chr1-113855166-C-T

Variant summary

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

The ENST00000359785.10(PTPN22):​c.541-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 862,672 control chromosomes in the GnomAD database, including 13,988 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 (2113 hom., cov: 32)
  • Exomes 𝑓: 0.18 (11875 hom.)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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 (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN22	NM_015967.8	c.541-117G>A		intron_variant		ENST00000359785.10
PTPN22	XM_047417630.1	c.469-117G>A		intron_variant
AP4B1-AS1	NR_125965.1	n.414+39694C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.541-117G>A		intron_variant		1	NM_015967.8	P1
	ENST00000664434.1	n.471-2817C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23759 AN: 151988 Hom.: 2112 Cov.: 32

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.178 AC: 126215 AN: 710566 Hom.: 11875 AF XY: 0.175 AC XY: 64186 AN XY: 366260

Gnomad4 AFR exome AF: 0.0766

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.156 AC: 23769 AN: 152106 Hom.: 2113 Cov.: 32 AF XY: 0.157 AC XY: 11688 AN XY: 74358

Gnomad4 AFR AF: 0.0819

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.166

Alfa AF: 0.169 Hom.: 743

Bravo AF: 0.153

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.79
DANN	Benign	0.51

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: rs3789608; hg19: chr1-114397788; COSMIC: COSV63084569; COSMIC: COSV63084569;