chr1-113858609-A-G

Variant names:

• chr1-113858609-A-G
• rs1217418
• NM_015967.8:c.274-36T>C

Variant summary

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

The NM_015967.8(PTPN22):​c.274-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,284,472 control chromosomes in the GnomAD database, including 205,272 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 0.56 (24715 hom., cov: 27)
  • Exomes 𝑓: 0.56 (180557 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 36 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.274-36T>C		intron_variant	Intron 3 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.274-36T>C		intron_variant	Intron 3 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85010 AN: 151234 Hom.: 24688 Cov.: 27

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.531 AC: 78253 AN: 147410 AF XY: 0.539

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.570

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.557 AC: 630651 AN: 1133126 Hom.: 180557 Cov.: 15 AF XY: 0.560 AC XY: 319173 AN XY: 569658

African (AFR) AF: 0.655 AC: 16519 AN: 25224

American (AMR) AF: 0.403 AC: 11317 AN: 28086

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 12939 AN: 21798

East Asian (EAS) AF: 0.185 AC: 6689 AN: 36212

South Asian (SAS) AF: 0.661 AC: 46477 AN: 70320

European-Finnish (FIN) AF: 0.500 AC: 24686 AN: 49342

Middle Eastern (MID) AF: 0.606 AC: 2127 AN: 3510

European-Non Finnish (NFE) AF: 0.568 AC: 482646 AN: 849858

Other (OTH) AF: 0.559 AC: 27251 AN: 48776

GnomAD4 genome AF: 0.562 AC: 85084 AN: 151346 Hom.: 24715 Cov.: 27 AF XY: 0.556 AC XY: 41154 AN XY: 73956

African (AFR) AF: 0.648 AC: 26674 AN: 41132

American (AMR) AF: 0.452 AC: 6879 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2104 AN: 3470

East Asian (EAS) AF: 0.161 AC: 831 AN: 5148

South Asian (SAS) AF: 0.652 AC: 3117 AN: 4782

European-Finnish (FIN) AF: 0.487 AC: 5085 AN: 10450

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.568 AC: 38544 AN: 67854

Other (OTH) AF: 0.544 AC: 1143 AN: 2102

Alfa AF: 0.568 Hom.: 15663

Bravo AF: 0.555

Asia WGS AF: 0.438 AC: 1524 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	0.70
DANN	Benign	0.46
PhyloP100		-0.10
Mutation Taster		=99/1	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: rs1217418; hg19: chr1-114401231; COSMIC: COSV63087307; COSMIC: COSV63087307;