1-113829906-T-G

Variant names:

• chr1-113829906-T-G
• rs3761935
• NM_015967.8:c.2134+43A>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.2134+43A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,500,234 control chromosomes in the GnomAD database, including 23,704 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 0.16 (2079 hom., cov: 32)
  • Exomes 𝑓: 0.18 (21625 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 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.2134+43A>C		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.2062+43A>C		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.2050+43A>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.2134+43A>C		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.2134+43A>C		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.2062+43A>C		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23591 AN: 151954 Hom.: 2078 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.170 AC: 41634 AN: 245176 AF XY: 0.169

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.176 AC: 236970 AN: 1348162 Hom.: 21625 Cov.: 24 AF XY: 0.174 AC XY: 117686 AN XY: 676076

African (AFR) AF: 0.0737 AC: 2269 AN: 30788

American (AMR) AF: 0.140 AC: 6191 AN: 44184

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3888 AN: 25446

East Asian (EAS) AF: 0.211 AC: 8206 AN: 38970

South Asian (SAS) AF: 0.116 AC: 9691 AN: 83350

European-Finnish (FIN) AF: 0.188 AC: 10025 AN: 53288

Middle Eastern (MID) AF: 0.119 AC: 661 AN: 5546

European-Non Finnish (NFE) AF: 0.185 AC: 186431 AN: 1009990

Other (OTH) AF: 0.170 AC: 9608 AN: 56600

GnomAD4 genome AF: 0.155 AC: 23601 AN: 152072 Hom.: 2079 Cov.: 32 AF XY: 0.156 AC XY: 11623 AN XY: 74336

African (AFR) AF: 0.0810 AC: 3365 AN: 41518

American (AMR) AF: 0.169 AC: 2580 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3466

East Asian (EAS) AF: 0.229 AC: 1180 AN: 5162

South Asian (SAS) AF: 0.117 AC: 565 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2085 AN: 10568

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12699 AN: 67952

Other (OTH) AF: 0.165 AC: 347 AN: 2106

Alfa AF: 0.129 Hom.: 454

Bravo AF: 0.152

Asia WGS AF: 0.191 AC: 663 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3761935; hg19: chr1-114372528; COSMIC: COSV63084534; COSMIC: COSV63084534;