rs1217420

Positions:

• chr1-113860129-A-G

Variant summary

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

The NM_015967.8(PTPN22):​c.88-669T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,732 control chromosomes in the GnomAD database, including 25,247 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 0.57 (25247 hom., cov: 29)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.88-669T>C		intron_variant			NP_057051.4
PTPN22	NM_001308297.1	c.88-669T>C		intron_variant			NP_001295226.2
PTPN22	NM_001193431.2	c.88-669T>C		intron_variant			NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.88-669T>C		intron_variant		1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85935 AN: 151614 Hom.: 25221 Cov.: 29

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.567 AC: 86015 AN: 151732 Hom.: 25247 Cov.: 29 AF XY: 0.561 AC XY: 41579 AN XY: 74104

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.546

Alfa AF: 0.572 Hom.: 3124

Bravo AF: 0.560

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.55

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: rs1217420; hg19: chr1-114402751;