rs3789607

Variant names:

• chr1-113823812-T-C
• rs3789607
• NM_015967.8:c.2281+1330A>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.2281+1330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,218 control chromosomes in the GnomAD database, including 4,502 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 0.22 (4502 hom., cov: 32)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988
• Publications: 26 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 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.2281+1330A>G		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.2209+1330A>G		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.2197+1330A>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.2281+1330A>G		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.2281+1330A>G		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.2209+1330A>G		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33083 AN: 152100 Hom.: 4503 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.217 AC: 33090 AN: 152218 Hom.: 4502 Cov.: 32 AF XY: 0.218 AC XY: 16213 AN XY: 74426

African (AFR) AF: 0.0602 AC: 2503 AN: 41570

American (AMR) AF: 0.231 AC: 3539 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3472

East Asian (EAS) AF: 0.0922 AC: 478 AN: 5184

South Asian (SAS) AF: 0.390 AC: 1877 AN: 4816

European-Finnish (FIN) AF: 0.248 AC: 2627 AN: 10584

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20149 AN: 67978

Other (OTH) AF: 0.246 AC: 521 AN: 2116

Alfa AF: 0.281 Hom.: 10312

Bravo AF: 0.207

Asia WGS AF: 0.239 AC: 833 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.99
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: rs3789607; hg19: chr1-114366434;