rs11582409

chr1-113856811-C-T

Variant summary

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

The ENST00000359785.10(PTPN22):c.409-192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 649,238 control chromosomes in the GnomAD database, including 9,925 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 (2110 hom., cov: 32)
  • Exomes 𝑓: 0.17 (7815 hom.)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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]

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

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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.409-192G>A		intron_variant		ENST00000359785.10
PTPN22	XM_047417630.1	c.409-370G>A		intron_variant
AP4B1-AS1	NR_125965.1	n.415-41057C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.409-192G>A		intron_variant		1	NM_015967.8	P1
AP4B1-AS1	ENST00000419536.1	n.90+87C>T		intron_variant, non_coding_transcript_variant		2
	ENST00000664434.1	n.471-1172C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23750 AN: 152054 Hom.: 2109 Cov.: 32

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.172 AC: 85557 AN: 497066 Hom.: 7815 Cov.: 7 AF XY: 0.169 AC XY: 43381 AN XY: 256248

Gnomad4 AFR exome AF: 0.0778

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.156 AC: 23760 AN: 152172 Hom.: 2110 Cov.: 32 AF XY: 0.157 AC XY: 11677 AN XY: 74358

Gnomad4 AFR AF: 0.0819

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.165

Alfa AF: 0.160 Hom.: 396

Bravo AF: 0.153

Asia WGS AF: 0.195 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.1
Dann	Benign	0.50

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: rs11582409; hg19: chr1-114399433; COSMIC: COSV63084576; COSMIC: COSV63084576;