rs34209542
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The ENST00000359785.10(PTPN22):c.2134+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,493,702 control chromosomes in the GnomAD database, including 439 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 0.017 ( 33 hom., cov: 32)
Exomes 𝑓: 0.022 ( 406 hom. )
Consequence
PTPN22
ENST00000359785.10 intron
ENST00000359785.10 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.174
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2581/152070) while in subpopulation NFE AF= 0.0257 (1746/67960). AF 95% confidence interval is 0.0247. There are 33 homozygotes in gnomad4. There are 1204 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN22 | NM_015967.8 | c.2134+47T>C | intron_variant | ENST00000359785.10 | |||
PTPN22 | XM_047417630.1 | c.1984+47T>C | intron_variant | ||||
AP4B1-AS1 | NR_125965.1 | n.414+14430A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN22 | ENST00000359785.10 | c.2134+47T>C | intron_variant | 1 | NM_015967.8 | P1 | |||
ENST00000664434.1 | n.419-1860A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0170 AC: 2583AN: 151952Hom.: 33 Cov.: 32
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GnomAD3 exomes AF: 0.0184 AC: 4496AN: 244244Hom.: 59 AF XY: 0.0192 AC XY: 2542AN XY: 132612
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GnomAD4 exome AF: 0.0224 AC: 30055AN: 1341632Hom.: 406 Cov.: 22 AF XY: 0.0221 AC XY: 14890AN XY: 673032
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GnomAD4 genome ? AF: 0.0170 AC: 2581AN: 152070Hom.: 33 Cov.: 32 AF XY: 0.0162 AC XY: 1204AN XY: 74338
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at