rs33965092

Positions:

• chr1-113834605-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015967.8(PTPN22):​c.1895-166G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 152,260 control chromosomes in the GnomAD database, including 48 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 0.021 (48 hom., cov: 32)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0207 (3147/152260) while in subpopulation NFE AF= 0.0297 (2019/68026). AF 95% confidence interval is 0.0286. There are 48 homozygotes in gnomad4. There are 1478 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.1895-166G>T		intron_variant			NP_057051.4
PTPN22	NM_001308297.2	c.1823-166G>T		intron_variant			NP_001295226.2
PTPN22	NM_001193431.3	c.1895-166G>T		intron_variant			NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.1895-166G>T		intron_variant		1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3145 AN: 152142 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.00656

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0207 AC: 3147 AN: 152260 Hom.: 48 Cov.: 32 AF XY: 0.0199 AC XY: 1478 AN XY: 74450

Gnomad4 AFR AF: 0.00655

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0242 Hom.: 4

Bravo AF: 0.0198

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.70

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: rs33965092; hg19: chr1-114377227;