rs1217414

Positions:

• chr1-113870045-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359785.10(PTPN22):​c.87+1492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,016 control chromosomes in the GnomAD database, including 11,875 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 0.36 (11875 hom., cov: 32)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393

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]

(HGNC:):

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.87+1492C>T		intron_variant		ENST00000359785.10	NP_057051.4
PTPN22	XM_047417630.1	c.87+1492C>T		intron_variant			XP_047273586.1
AP4B1-AS1	NR_125965.1	n.415-27823G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.87+1492C>T		intron_variant		1	NM_015967.8	ENSP00000352833	P1
	ENST00000664434.1	n.688G>A		non_coding_transcript_exon_variant	6/6
AP4B1-AS1	ENST00000419536.1	n.246+12029G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53894 AN: 151898 Hom.: 11849 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.355 AC: 53966 AN: 152016 Hom.: 11875 Cov.: 32 AF XY: 0.348 AC XY: 25875 AN XY: 74310

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.0770

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.307

Alfa AF: 0.304 Hom.: 2194

Bravo AF: 0.359

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1217414; hg19: chr1-114412667;