rs1217419

Variant names:

• chr1-113859282-T-G
• rs1217419
• NM_015967.8:c.196+70A>C

Variant summary

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

The NM_015967.8(PTPN22):​c.196+70A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,543,506 control chromosomes in the GnomAD database, including 245,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.56 (24542 hom., cov: 32)
  • Exomes 𝑓: 0.56 (221264 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 17 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 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.196+70A>C		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.196+70A>C		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.196+70A>C		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.196+70A>C		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.196+70A>C		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.196+70A>C		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84931 AN: 151896 Hom.: 24518 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.558 AC: 775914 AN: 1391492 Hom.: 221264 Cov.: 23 AF XY: 0.561 AC XY: 389497 AN XY: 693754

African (AFR) AF: 0.644 AC: 20253 AN: 31466

American (AMR) AF: 0.387 AC: 16167 AN: 41806

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 14792 AN: 24852

East Asian (EAS) AF: 0.184 AC: 7199 AN: 39140

South Asian (SAS) AF: 0.659 AC: 55018 AN: 83426

European-Finnish (FIN) AF: 0.501 AC: 26300 AN: 52458

Middle Eastern (MID) AF: 0.607 AC: 2768 AN: 4562

European-Non Finnish (NFE) AF: 0.569 AC: 601094 AN: 1056106

Other (OTH) AF: 0.560 AC: 32323 AN: 57676

GnomAD4 genome AF: 0.559 AC: 85005 AN: 152014 Hom.: 24542 Cov.: 32 AF XY: 0.553 AC XY: 41124 AN XY: 74304

African (AFR) AF: 0.638 AC: 26437 AN: 41446

American (AMR) AF: 0.451 AC: 6884 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2104 AN: 3472

East Asian (EAS) AF: 0.162 AC: 835 AN: 5170

South Asian (SAS) AF: 0.651 AC: 3146 AN: 4830

European-Finnish (FIN) AF: 0.489 AC: 5157 AN: 10552

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38588 AN: 67970

Other (OTH) AF: 0.543 AC: 1143 AN: 2104

Alfa AF: 0.551 Hom.: 5404

Bravo AF: 0.551

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.41
PhyloP100		-0.077
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: rs1217419; hg19: chr1-114401904; COSMIC: COSV63084918;