rs17510162

Variant names:

• chr1-113871109-C-A
• rs17510162
• NM_015967.8:c.87+428G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015967.8(PTPN22):​c.87+428G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,060 control chromosomes in the GnomAD database, including 2,021 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 0.15 (2021 hom., cov: 32)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.905
• Publications: 15 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015967.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.87+428G>T		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.87+428G>T		intron	N/A	NP_001295226.2
	PTPN22	NM_001193431.3		c.87+428G>T		intron	N/A	NP_001180360.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.87+428G>T		intron	N/A	ENSP00000352833.5
	PTPN22	ENST00000420377.6	TSL:1	c.87+428G>T		intron	N/A	ENSP00000388229.2
	PTPN22	ENST00000538253.5	TSL:1	c.87+428G>T		intron	N/A	ENSP00000439372.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23304 AN: 151942 Hom.: 2018 Cov.: 32

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.153 AC: 23315 AN: 152060 Hom.: 2021 Cov.: 32 AF XY: 0.155 AC XY: 11516 AN XY: 74324

African (AFR) AF: 0.0814 AC: 3378 AN: 41510

American (AMR) AF: 0.165 AC: 2519 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1144 AN: 5168

South Asian (SAS) AF: 0.117 AC: 563 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2085 AN: 10534

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12492 AN: 67968

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.160 Hom.: 920

Bravo AF: 0.149

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.37
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17510162; hg19: chr1-114413731;