rs1217416

Variant names:

• chr1-113858182-C-T
• rs1217416
• ENST00000359785.10:c.369+296G>A

Variant summary

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

The ENST00000359785.10(PTPN22):​c.369+296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,060 control chromosomes in the GnomAD database, including 50,323 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 (50323 hom., cov: 31)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.369+296G>A		intron_variant	Intron 4 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.369+296G>A		intron_variant	Intron 4 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.369+296G>A		intron_variant	Intron 4 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.369+296G>A		intron_variant	Intron 4 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122408 AN: 151942 Hom.: 50265 Cov.: 31

Gnomad AFR AF: 0.947

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: 0.696

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.806 AC: 122524 AN: 152060 Hom.: 50323 Cov.: 31 AF XY: 0.801 AC XY: 59478 AN XY: 74296

African (AFR) AF: 0.947 AC: 39317 AN: 41524

American (AMR) AF: 0.734 AC: 11195 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2783 AN: 3468

East Asian (EAS) AF: 0.414 AC: 2135 AN: 5162

South Asian (SAS) AF: 0.823 AC: 3974 AN: 4826

European-Finnish (FIN) AF: 0.696 AC: 7334 AN: 10534

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.781 AC: 53107 AN: 67974

Other (OTH) AF: 0.785 AC: 1656 AN: 2110

Alfa AF: 0.793 Hom.: 6006

Bravo AF: 0.806

Asia WGS AF: 0.678 AC: 2359 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	0.26
DANN	Benign	0.20
PhyloP100		-1.7
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: rs1217416; hg19: chr1-114400804;