rs1217403

Variant names:

• chr1-113846182-T-C
• rs1217403
• NM_015967.8:c.915+2358A>G

Variant summary

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

The NM_015967.8(PTPN22):​c.915+2358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,016 control chromosomes in the GnomAD database, including 9,296 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 0.32 (9296 hom., cov: 33)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 14 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.915+2358A>G		intron_variant	Intron 11 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.915+2358A>G		intron_variant	Intron 11 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48303 AN: 151898 Hom.: 9275 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.318 AC: 48367 AN: 152016 Hom.: 9296 Cov.: 33 AF XY: 0.312 AC XY: 23179 AN XY: 74294

African (AFR) AF: 0.536 AC: 22168 AN: 41392

American (AMR) AF: 0.203 AC: 3096 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3470

East Asian (EAS) AF: 0.0655 AC: 340 AN: 5194

South Asian (SAS) AF: 0.254 AC: 1229 AN: 4834

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10570

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17409 AN: 67956

Other (OTH) AF: 0.266 AC: 562 AN: 2112

Alfa AF: 0.289 Hom.: 1581

Bravo AF: 0.322

Asia WGS AF: 0.174 AC: 603 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.3
DANN	Benign	0.92
PhyloP100		0.14
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: rs1217403; hg19: chr1-114388804;