chr1-113840475-A-C

Variant names:

• chr1-113840475-A-C
• rs1746853
• NM_015967.8:c.916-1855T>G

Variant summary

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

The NM_015967.8(PTPN22):​c.916-1855T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,988 control chromosomes in the GnomAD database, including 18,386 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 0.48 (18386 hom., cov: 32)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 12 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 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.916-1855T>G		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.844-1855T>G		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.916-1855T>G		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.916-1855T>G		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.916-1855T>G		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.844-1855T>G		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72798 AN: 151870 Hom.: 18358 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.479 AC: 72876 AN: 151988 Hom.: 18386 Cov.: 32 AF XY: 0.475 AC XY: 35257 AN XY: 74296

African (AFR) AF: 0.636 AC: 26358 AN: 41450

American (AMR) AF: 0.375 AC: 5735 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1549 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1522 AN: 5160

South Asian (SAS) AF: 0.373 AC: 1802 AN: 4828

European-Finnish (FIN) AF: 0.407 AC: 4291 AN: 10534

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.443 AC: 30132 AN: 67960

Other (OTH) AF: 0.431 AC: 903 AN: 2094

Alfa AF: 0.339 Hom.: 918

Bravo AF: 0.480

Asia WGS AF: 0.367 AC: 1273 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		0.34
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: rs1746853; hg19: chr1-114383097;