1-113830881-A-G

Variant names:

• chr1-113830881-A-G
• rs1310182
• NM_015967.8:c.2054-852T>C

Variant summary

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

The NM_015967.8(PTPN22):​c.2054-852T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,918 control chromosomes in the GnomAD database, including 24,555 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 0.56 (24555 hom., cov: 32)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 44 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 = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015967.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.2054-852T>C		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.1982-852T>C		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.1970-852T>C		intron	N/A	NP_001180360.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.2054-852T>C		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.2054-852T>C		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.1982-852T>C		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84931 AN: 151800 Hom.: 24531 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.560 AC: 85004 AN: 151918 Hom.: 24555 Cov.: 32 AF XY: 0.554 AC XY: 41099 AN XY: 74246

African (AFR) AF: 0.638 AC: 26448 AN: 41454

American (AMR) AF: 0.451 AC: 6896 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2109 AN: 3466

East Asian (EAS) AF: 0.160 AC: 830 AN: 5182

South Asian (SAS) AF: 0.651 AC: 3138 AN: 4818

European-Finnish (FIN) AF: 0.487 AC: 5140 AN: 10546

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38589 AN: 67868

Other (OTH) AF: 0.543 AC: 1144 AN: 2106

Alfa AF: 0.504 Hom.: 3635

Bravo AF: 0.552

Asia WGS AF: 0.435 AC: 1509 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.90
DANN	Benign	0.69
PhyloP100		-0.58
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: rs1310182; hg19: chr1-114373503;