1-113834526-T-C

Variant names:

• chr1-113834526-T-C
• rs1970559
• ENST00000359785.10:c.1895-87A>G

Variant summary

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

The NM_015967.8(PTPN22):​c.1895-87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,348,560 control chromosomes in the GnomAD database, including 56,735 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 0.34 (10811 hom., cov: 32)
  • Exomes 𝑓: 0.27 (45924 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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]

ENSG00000231128 (HGNC:):

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.1895-87A>G		intron_variant	Intron 14 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.1823-87A>G		intron_variant	Intron 13 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.1895-87A>G		intron_variant	Intron 14 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.1895-87A>G		intron_variant	Intron 14 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51956 AN: 151982 Hom.: 10789 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.270 AC: 322796 AN: 1196460 Hom.: 45924 AF XY: 0.270 AC XY: 162970 AN XY: 604344

Gnomad4 AFR exome AF: 0.593

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.0946

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.342 AC: 52022 AN: 152100 Hom.: 10811 Cov.: 32 AF XY: 0.336 AC XY: 24954 AN XY: 74352

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.0680

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.298

Alfa AF: 0.295 Hom.: 1637

Bravo AF: 0.345

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.53

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: rs1970559; hg19: chr1-114377148; COSMIC: COSV63085369;