rs1217389

Variant names:

• chr1-113823130-C-T
• rs1217389
• NM_015967.8:c.2281+2012G>A

Variant summary

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

The NM_015967.8(PTPN22):​c.2281+2012G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 151,866 control chromosomes in the GnomAD database, including 44,692 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 0.76 (44689 hom., cov: 32)
  • Exomes 𝑓: 0.64 (3 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2281+2012G>A		intron_variant	Intron 19 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2281+2012G>A		intron_variant	Intron 19 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115466 AN: 151734 Hom.: 44641 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.643 AC: 9 AN: 14 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 8 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.800 AC: 8 AN: 10

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.761 AC: 115575 AN: 151852 Hom.: 44689 Cov.: 32 AF XY: 0.754 AC XY: 55999 AN XY: 74224

African (AFR) AF: 0.879 AC: 36272 AN: 41284

American (AMR) AF: 0.639 AC: 9733 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2647 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2021 AN: 5182

South Asian (SAS) AF: 0.770 AC: 3707 AN: 4816

European-Finnish (FIN) AF: 0.687 AC: 7253 AN: 10556

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51423 AN: 67994

Other (OTH) AF: 0.741 AC: 1560 AN: 2106

Alfa AF: 0.758 Hom.: 53870

Bravo AF: 0.753

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.8
DANN	Benign	0.43
PhyloP100		0.39
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: rs1217389; hg19: chr1-114365752;