chr1-113853658-T-C

Variant names:

• chr1-113853658-T-C
• rs1217408
• ENST00000359785.10:c.750+813A>G

Variant summary

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

The ENST00000359785.10(PTPN22):​c.750+813A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 150,680 control chromosomes in the GnomAD database, including 10,733 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 0.34 (10733 hom., cov: 29)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.750+813A>G		intron_variant	Intron 9 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.678+813A>G		intron_variant	Intron 8 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.750+813A>G		intron_variant	Intron 9 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.750+813A>G		intron_variant	Intron 9 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51626 AN: 150564 Hom.: 10710 Cov.: 29

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.273

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.343 AC: 51694 AN: 150680 Hom.: 10733 Cov.: 29 AF XY: 0.337 AC XY: 24812 AN XY: 73626

African (AFR) AF: 0.579 AC: 23847 AN: 41168

American (AMR) AF: 0.221 AC: 3348 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1071 AN: 3456

East Asian (EAS) AF: 0.0686 AC: 343 AN: 5000

South Asian (SAS) AF: 0.267 AC: 1276 AN: 4772

European-Finnish (FIN) AF: 0.239 AC: 2466 AN: 10312

Middle Eastern (MID) AF: 0.269 AC: 77 AN: 286

European-Non Finnish (NFE) AF: 0.272 AC: 18372 AN: 67524

Other (OTH) AF: 0.300 AC: 626 AN: 2090

Alfa AF: 0.220 Hom.: 584

Bravo AF: 0.345

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.30
PhyloP100		0.19
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: rs1217408; hg19: chr1-114396280;