1-113834526-T-C

Variant names:

• chr1-113834526-T-C
• rs1970559
• NM_015967.8:c.1895-87A>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.1895-87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,348,560 control chromosomes in the GnomAD database, including 56,735 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 (10811 hom., cov: 32)
  • Exomes 𝑓: 0.27 (45924 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 22 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 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.1895-87A>G		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.1823-87A>G		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.1895-87A>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.1895-87A>G		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.1895-87A>G		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.1823-87A>G		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51956 AN: 151982 Hom.: 10789 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.270 AC: 322796 AN: 1196460 Hom.: 45924 AF XY: 0.270 AC XY: 162970 AN XY: 604344

African (AFR) AF: 0.593 AC: 16134 AN: 27188

American (AMR) AF: 0.150 AC: 5797 AN: 38662

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 7047 AN: 22454

East Asian (EAS) AF: 0.0946 AC: 3623 AN: 38316

South Asian (SAS) AF: 0.280 AC: 21134 AN: 75424

European-Finnish (FIN) AF: 0.255 AC: 13027 AN: 51160

Middle Eastern (MID) AF: 0.276 AC: 1337 AN: 4838

European-Non Finnish (NFE) AF: 0.271 AC: 240456 AN: 887232

Other (OTH) AF: 0.278 AC: 14241 AN: 51186

GnomAD4 genome AF: 0.342 AC: 52022 AN: 152100 Hom.: 10811 Cov.: 32 AF XY: 0.336 AC XY: 24954 AN XY: 74352

African (AFR) AF: 0.578 AC: 23960 AN: 41474

American (AMR) AF: 0.220 AC: 3358 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1081 AN: 3472

East Asian (EAS) AF: 0.0680 AC: 352 AN: 5178

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2520 AN: 10566

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

European-Non Finnish (NFE) AF: 0.272 AC: 18513 AN: 67986

Other (OTH) AF: 0.298 AC: 628 AN: 2110

Alfa AF: 0.301 Hom.: 1767

Bravo AF: 0.345

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.53
PhyloP100		-2.0
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: rs1970559; hg19: chr1-114377148; COSMIC: COSV63085369;