chr1-113814041-A-G

Position:

• chr1-113814041-A-G

Variant summary

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

The ENST00000359785.10(PTPN22):​c.*864T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,316 control chromosomes in the GnomAD database, including 2,085 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 0.16 (2085 hom., cov: 33)
  • Exomes 𝑓: 0.098 (0 hom.)
• Consequence: PTPN22 ENST00000359785.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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]

(HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN22	NM_015967.8	c.*864T>C		3_prime_UTR_variant	21/21	ENST00000359785.10
PTPN22	XM_047417630.1	c.*864T>C		3_prime_UTR_variant	19/19
AP4B1-AS1	NR_125965.1	n.215-346A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.*864T>C		3_prime_UTR_variant	21/21	1	NM_015967.8	P1
	ENST00000664434.1	n.219-346A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23620 AN: 152076 Hom.: 2084 Cov.: 33

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0984 AC: 12 AN: 122 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 6 AN XY: 72

Gnomad4 EAS exome AF: 0.0984

GnomAD4 genome AF: 0.155 AC: 23630 AN: 152194 Hom.: 2085 Cov.: 33 AF XY: 0.156 AC XY: 11628 AN XY: 74400

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.164

Alfa AF: 0.178 Hom.: 2578

Bravo AF: 0.152

Asia WGS AF: 0.191 AC: 659 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.65

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: rs3811021; hg19: chr1-114356663;