chr1-113860224-G-C

Variant names:

• chr1-113860224-G-C
• rs1217421
• NM_015967.8:c.88-764C>G

Variant summary

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

The NM_015967.8(PTPN22):​c.88-764C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,058 control chromosomes in the GnomAD database, including 45,730 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 0.77 (45730 hom., cov: 31)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.88-764C>G		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.88-764C>G		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.88-764C>G		intron	N/A	NP_001180360.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.88-764C>G		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.88-764C>G		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.88-764C>G		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116612 AN: 151940 Hom.: 45676 Cov.: 31

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.768 AC: 116727 AN: 152058 Hom.: 45730 Cov.: 31 AF XY: 0.761 AC XY: 56549 AN XY: 74320

African (AFR) AF: 0.900 AC: 37373 AN: 41508

American (AMR) AF: 0.642 AC: 9787 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2022 AN: 5168

South Asian (SAS) AF: 0.770 AC: 3717 AN: 4826

European-Finnish (FIN) AF: 0.686 AC: 7235 AN: 10540

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51419 AN: 67980

Other (OTH) AF: 0.743 AC: 1567 AN: 2108

Alfa AF: 0.759 Hom.: 5177

Bravo AF: 0.762

Asia WGS AF: 0.642 AC: 2235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		-0.38
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: rs1217421; hg19: chr1-114402846;