rs34209542

Positions:

• chr1-113829902-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000359785.10(PTPN22):​c.2134+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,493,702 control chromosomes in the GnomAD database, including 439 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 0.017 (33 hom., cov: 32)
  • Exomes 𝑓: 0.022 (406 hom.)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2581/152070) while in subpopulation NFE AF= 0.0257 (1746/67960). AF 95% confidence interval is 0.0247. There are 33 homozygotes in gnomad4. There are 1204 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2134+47T>C		intron_variant		ENST00000359785.10	NP_057051.4
PTPN22	XM_047417630.1	c.1984+47T>C		intron_variant			XP_047273586.1
AP4B1-AS1	NR_125965.1	n.414+14430A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2134+47T>C		intron_variant		1	NM_015967.8	ENSP00000352833	P1
	ENST00000664434.1	n.419-1860A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2583 AN: 151952 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0226

GnomAD3 exomes AF: 0.0184 AC: 4496 AN: 244244 Hom.: 59 AF XY: 0.0192 AC XY: 2542 AN XY: 132612

Gnomad AFR exome AF: 0.00470

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.0161

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.0177

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0199

GnomAD4 exome AF: 0.0224 AC: 30055 AN: 1341632 Hom.: 406 Cov.: 22 AF XY: 0.0221 AC XY: 14890 AN XY: 673032

Gnomad4 AFR exome AF: 0.00383

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.0000771

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.0199

Gnomad4 NFE exome AF: 0.0251

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0170 AC: 2581 AN: 152070 Hom.: 33 Cov.: 32 AF XY: 0.0162 AC XY: 1204 AN XY: 74338

Gnomad4 AFR AF: 0.00487

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0213 Hom.: 15

Bravo AF: 0.0158

Asia WGS AF: 0.00549 AC: 19 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34209542; hg19: chr1-114372524;