rs12760457

Variant names:

• chr1-113847126-C-T
• rs12760457
• NM_015967.8:c.915+1414G>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.915+1414G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 149,190 control chromosomes in the GnomAD database, including 4,414 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 0.22 (4414 hom., cov: 27)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 25 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 (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.915+1414G>A		intron_variant	Intron 11 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.915+1414G>A		intron_variant	Intron 11 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32436 AN: 149078 Hom.: 4415 Cov.: 27

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0921

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.217 AC: 32440 AN: 149190 Hom.: 4414 Cov.: 27 AF XY: 0.218 AC XY: 15838 AN XY: 72722

African (AFR) AF: 0.0592 AC: 2415 AN: 40760

American (AMR) AF: 0.233 AC: 3477 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1031 AN: 3454

East Asian (EAS) AF: 0.0921 AC: 470 AN: 5104

South Asian (SAS) AF: 0.391 AC: 1849 AN: 4734

European-Finnish (FIN) AF: 0.246 AC: 2346 AN: 9532

Middle Eastern (MID) AF: 0.339 AC: 97 AN: 286

European-Non Finnish (NFE) AF: 0.296 AC: 19979 AN: 67438

Other (OTH) AF: 0.246 AC: 512 AN: 2078

Alfa AF: 0.237 Hom.: 1201

Bravo AF: 0.206

Asia WGS AF: 0.237 AC: 823 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.42
PhyloP100		0.14
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: rs12760457; hg19: chr1-114389748;