NM_015967.8:c.88-2819G>A

Variant names:

• chr1-113862279-C-T
• rs1775754
• NM_015967.8:c.88-2819G>A

Variant summary

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

The NM_015967.8(PTPN22):​c.88-2819G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 151,746 control chromosomes in the GnomAD database, including 45,649 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 (45649 hom., cov: 29)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.88-2819G>A		intron_variant	Intron 1 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.88-2819G>A		intron_variant	Intron 1 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116425 AN: 151630 Hom.: 45595 Cov.: 29

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.768 AC: 116540 AN: 151746 Hom.: 45649 Cov.: 29 AF XY: 0.761 AC XY: 56431 AN XY: 74128

African (AFR) AF: 0.900 AC: 37233 AN: 41364

American (AMR) AF: 0.642 AC: 9781 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2023 AN: 5148

South Asian (SAS) AF: 0.771 AC: 3709 AN: 4808

European-Finnish (FIN) AF: 0.688 AC: 7207 AN: 10478

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.757 AC: 51412 AN: 67946

Other (OTH) AF: 0.745 AC: 1568 AN: 2106

Alfa AF: 0.759 Hom.: 5178

Bravo AF: 0.762

Asia WGS AF: 0.642 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.35
PhyloP100		-1.2
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: rs1775754; hg19: chr1-114404901;