1-113858282-C-G

Variant names:

• chr1-113858282-C-G
• rs1217417
• ENST00000359785.10:c.369+196G>C

Variant summary

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

The ENST00000359785.10(PTPN22):​c.369+196G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,744 control chromosomes in the GnomAD database, including 9,326 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 0.32 (9326 hom., cov: 31)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 6 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 = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.369+196G>C		intron_variant	Intron 4 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.369+196G>C		intron_variant	Intron 4 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.369+196G>C		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+196G>C		intron_variant	Intron 4 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48266 AN: 151626 Hom.: 9305 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.318 AC: 48330 AN: 151744 Hom.: 9326 Cov.: 31 AF XY: 0.313 AC XY: 23178 AN XY: 74134

African (AFR) AF: 0.537 AC: 22202 AN: 41364

American (AMR) AF: 0.203 AC: 3090 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1004 AN: 3464

East Asian (EAS) AF: 0.0652 AC: 334 AN: 5124

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4810

European-Finnish (FIN) AF: 0.212 AC: 2232 AN: 10534

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17347 AN: 67890

Other (OTH) AF: 0.266 AC: 560 AN: 2106

Alfa AF: 0.292 Hom.: 880

Bravo AF: 0.322

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.56
DANN	Benign	0.31
PhyloP100		-0.87
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: rs1217417; hg19: chr1-114400904;