chr1-113870045-G-A

Variant names:

• chr1-113870045-G-A
• rs1217414
• NM_015967.8:c.87+1492C>T

Variant summary

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

The NM_015967.8(PTPN22):​c.87+1492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,016 control chromosomes in the GnomAD database, including 11,875 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 0.36 (11875 hom., cov: 32)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 52 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 = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015967.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.87+1492C>T		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.87+1492C>T		intron	N/A	NP_001295226.2
	PTPN22	NM_001193431.3		c.87+1492C>T		intron	N/A	NP_001180360.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.87+1492C>T		intron	N/A	ENSP00000352833.5
	PTPN22	ENST00000420377.6	TSL:1	c.87+1492C>T		intron	N/A	ENSP00000388229.2
	PTPN22	ENST00000538253.5	TSL:1	c.87+1492C>T		intron	N/A	ENSP00000439372.2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53894 AN: 151898 Hom.: 11849 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.355 AC: 53966 AN: 152016 Hom.: 11875 Cov.: 32 AF XY: 0.348 AC XY: 25875 AN XY: 74310

African (AFR) AF: 0.617 AC: 25546 AN: 41436

American (AMR) AF: 0.226 AC: 3457 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3466

East Asian (EAS) AF: 0.0770 AC: 399 AN: 5182

South Asian (SAS) AF: 0.261 AC: 1256 AN: 4804

European-Finnish (FIN) AF: 0.239 AC: 2524 AN: 10552

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18719 AN: 67976

Other (OTH) AF: 0.307 AC: 647 AN: 2110

Alfa AF: 0.312 Hom.: 2559

Bravo AF: 0.359

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.59
PhyloP100		0.39
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: rs1217414; hg19: chr1-114412667;