rs3789607

chr1-113823812-T-C

Variant summary

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

The ENST00000359785.10(PTPN22):c.2281+1330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,218 control chromosomes in the GnomAD database, including 4,502 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 0.22 (4502 hom., cov: 32)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN22	NM_015967.8	c.2281+1330A>G		intron_variant		ENST00000359785.10
PTPN22	XM_047417630.1	c.2131+1330A>G		intron_variant
AP4B1-AS1	NR_125965.1	n.414+8340T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.2281+1330A>G		intron_variant		1	NM_015967.8	P1
	ENST00000664434.1	n.419-7950T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33083 AN: 152100 Hom.: 4503 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.217 AC: 33090 AN: 152218 Hom.: 4502 Cov.: 32 AF XY: 0.218 AC XY: 16213 AN XY: 74426

Gnomad4 AFR AF: 0.0602

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.246

Alfa AF: 0.290 Hom.: 8510

Bravo AF: 0.207

Asia WGS AF: 0.239 AC: 833 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	10
Dann	Benign	0.82

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: rs3789607; hg19: chr1-114366434;