rs1217412

Variant names:

• chr1-113814589-G-A
• rs1217412
• ENST00000359785.10:c.*316C>T

Variant summary

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

The ENST00000359785.10(PTPN22):​c.*316C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 214,238 control chromosomes in the GnomAD database, including 62,567 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 (45707 hom., cov: 32)
  • Exomes 𝑓: 0.73 (16860 hom.)
• Consequence: PTPN22 ENST00000359785.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 21 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.*316C>T		3_prime_UTR_variant	Exon 21 of 21		NP_057051.4
PTPN22	NM_001308297.2	c.*316C>T		3_prime_UTR_variant	Exon 20 of 20		NP_001295226.2
PTPN22	NM_001193431.3	c.*316C>T		3_prime_UTR_variant	Exon 21 of 21		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.*316C>T		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116561 AN: 151818 Hom.: 45654 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.728 AC: 45330 AN: 62302 Hom.: 16860 Cov.: 0 AF XY: 0.728 AC XY: 24200 AN XY: 33236

African (AFR) AF: 0.914 AC: 1265 AN: 1384

American (AMR) AF: 0.567 AC: 1660 AN: 2928

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 1384 AN: 1840

East Asian (EAS) AF: 0.395 AC: 1134 AN: 2872

South Asian (SAS) AF: 0.757 AC: 5133 AN: 6784

European-Finnish (FIN) AF: 0.684 AC: 1522 AN: 2226

Middle Eastern (MID) AF: 0.739 AC: 173 AN: 234

European-Non Finnish (NFE) AF: 0.751 AC: 30227 AN: 40238

Other (OTH) AF: 0.746 AC: 2832 AN: 3796

GnomAD4 genome AF: 0.768 AC: 116675 AN: 151936 Hom.: 45707 Cov.: 32 AF XY: 0.761 AC XY: 56510 AN XY: 74220

African (AFR) AF: 0.900 AC: 37381 AN: 41516

American (AMR) AF: 0.641 AC: 9787 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2647 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2026 AN: 5172

South Asian (SAS) AF: 0.770 AC: 3719 AN: 4832

European-Finnish (FIN) AF: 0.688 AC: 7210 AN: 10476

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

European-Non Finnish (NFE) AF: 0.757 AC: 51371 AN: 67892

Other (OTH) AF: 0.745 AC: 1573 AN: 2112

Alfa AF: 0.761 Hom.: 31759

Bravo AF: 0.762

Asia WGS AF: 0.635 AC: 2194 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.087
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: rs1217412; hg19: chr1-114357211;