chr1-113863380-G-A

Variant names:

• chr1-113863380-G-A
• rs2243471
• NM_015967.8:c.88-3920C>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.88-3920C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,250 control chromosomes in the GnomAD database, including 50,760 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 0.81 (50760 hom., cov: 33)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• Publications: 4 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.88-3920C>T		intron_variant	Intron 1 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.88-3920C>T		intron_variant	Intron 1 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122947 AN: 152132 Hom.: 50697 Cov.: 33

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.808 AC: 123068 AN: 152250 Hom.: 50760 Cov.: 33 AF XY: 0.803 AC XY: 59743 AN XY: 74422

African (AFR) AF: 0.956 AC: 39760 AN: 41572

American (AMR) AF: 0.734 AC: 11234 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2783 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2139 AN: 5172

South Asian (SAS) AF: 0.824 AC: 3975 AN: 4826

European-Finnish (FIN) AF: 0.695 AC: 7350 AN: 10576

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53138 AN: 68016

Other (OTH) AF: 0.787 AC: 1663 AN: 2114

Alfa AF: 0.794 Hom.: 6137

Bravo AF: 0.809

Asia WGS AF: 0.679 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.59
PhyloP100		-0.72
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: rs2243471; hg19: chr1-114406002;