1-113829710-TAAA-TAAAA

Variant names:

• chr1-113829710-T-TA
• rs57877024
• ENST00000359785.10:c.2135-4_2135-3insT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_015967.8(PTPN22):​c.2135-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: PTPN22 NM_015967.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0163 (17930/1098362) while in subpopulation EAS AF= 0.0412 (1314/31916). AF 95% confidence interval is 0.0393. There are 0 homozygotes in gnomad4_exome. There are 8817 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2135-4dupT		splice_region_variant, intron_variant	Intron 17 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.2063-4dupT		splice_region_variant, intron_variant	Intron 16 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.2051-4dupT		splice_region_variant, intron_variant	Intron 17 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2135-4_2135-3insT		splice_region_variant, intron_variant	Intron 17 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 16 AN: 147114 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.000763

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000750

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0163 AC: 17930 AN: 1098362 Hom.: 0 Cov.: 0 AF XY: 0.0159 AC XY: 8817 AN XY: 553520

Gnomad4 AFR exome AF: 0.00969

Gnomad4 AMR exome AF: 0.0203

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.0412

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.000109 AC: 16 AN: 147194 Hom.: 0 Cov.: 0 AF XY: 0.000112 AC XY: 8 AN XY: 71558

Gnomad4 AFR AF: 0.0000495

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.000763

Gnomad4 NFE AF: 0.0000751

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs57877024; hg19: chr1-114372332;