1-113829710-TA-T

Variant names:

• chr1-113829710-TA-T
• rs57877024
• ENST00000359785.10:c.2135-4delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000359785.10(PTPN22):​c.2135-4delT 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24361 hom., cov: 0)
  • Exomes 𝑓: 0.48 (38879 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPN22 ENST00000359785.10 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.68
• Publications: 4 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 -10 ACMG points.

• BP6: Variant 1-113829710-TA-T is Benign according to our data. Variant chr1-113829710-TA-T is described in ClinVar as [Benign]. Clinvar id is 769239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2135-4delT		splice_region_variant, intron_variant	Intron 17 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.2063-4delT		splice_region_variant, intron_variant	Intron 16 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.2051-4delT		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.2135-4delT		splice_region_variant, intron_variant	Intron 17 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.570 AC: 83756 AN: 146898 Hom.: 24341 Cov.: 0

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.591

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.552

GnomAD2 exomes AF: 0.524 AC: 78586 AN: 149926 AF XY: 0.525

Gnomad AFR exome AF: 0.588

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.396

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.539

Gnomad OTH exome AF: 0.525

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.480 AC: 515139 AN: 1073118 Hom.: 38879 Cov.: 0 AF XY: 0.482 AC XY: 260719 AN XY: 540598

African (AFR) AF: 0.522 AC: 12016 AN: 23036

American (AMR) AF: 0.450 AC: 11780 AN: 26204

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 9634 AN: 19424

East Asian (EAS) AF: 0.348 AC: 9671 AN: 27768

South Asian (SAS) AF: 0.512 AC: 32789 AN: 64014

European-Finnish (FIN) AF: 0.478 AC: 19115 AN: 40006

Middle Eastern (MID) AF: 0.502 AC: 2025 AN: 4032

European-Non Finnish (NFE) AF: 0.481 AC: 396257 AN: 823592

Other (OTH) AF: 0.485 AC: 21852 AN: 45042

GnomAD4 genome AF: 0.570 AC: 83817 AN: 146980 Hom.: 24361 Cov.: 0 AF XY: 0.565 AC XY: 40327 AN XY: 71428

African (AFR) AF: 0.665 AC: 26833 AN: 40328

American (AMR) AF: 0.459 AC: 6732 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2088 AN: 3426

East Asian (EAS) AF: 0.163 AC: 818 AN: 5010

South Asian (SAS) AF: 0.655 AC: 3057 AN: 4666

European-Finnish (FIN) AF: 0.492 AC: 4494 AN: 9138

Middle Eastern (MID) AF: 0.612 AC: 175 AN: 286

European-Non Finnish (NFE) AF: 0.571 AC: 37966 AN: 66522

Other (OTH) AF: 0.549 AC: 1122 AN: 2044

Alfa AF: 0.365 Hom.: 684

Bravo AF: 0.558

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 30, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
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: rs57877024; hg19: chr1-114372332; COSMIC: COSV63084547; COSMIC: COSV63084547;