1-113854333-G-T

Variant names:

• chr1-113854333-G-T
• rs2476602
• NM_015967.8:c.750+138C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015967.8(PTPN22):​c.750+138C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 16 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.750+138C>A		intron_variant	Intron 9 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.750+138C>A		intron_variant	Intron 9 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 638396 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 331318

African (AFR) AF: 0.00 AC: 0 AN: 15978

American (AMR) AF: 0.00 AC: 0 AN: 25038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16022

East Asian (EAS) AF: 0.00 AC: 0 AN: 32272

South Asian (SAS) AF: 0.00 AC: 0 AN: 51600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3410

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 417658

Other (OTH) AF: 0.00 AC: 0 AN: 32394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2004

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.60
PhyloP100		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs2476602; hg19: chr1-114396955;