Variant 1-113829710-TAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The ENST00000359785.10(PTPN22):c.2135-5_2135-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,210,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 0)

Exomes 𝑓: 0.024 ( 0 hom. )

Consequence

PTPN22
ENST00000359785.10 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

Variant links:

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]

PTPN22 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 1-113829710-TAA-T is Benign according to our data. Variant chr1-113829710-TAA-T is described in ClinVar as [Benign]. Clinvar id is 775137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0243 (25843/1063444) while in subpopulation SAS AF= 0.0462 (2775/60122). AF 95% confidence interval is 0.0447. There are 0 homozygotes in gnomad4_exome. There are 13188 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PTPN22	NM_015967.8 linkuse as main transcript	c.2135-5_2135-4del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000359785.10
PTPN22	XM_047417630.1 linkuse as main transcript	c.1985-5_1985-4del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AP4B1-AS1	NR_125965.1 linkuse as main transcript	n.414+14249_414+14250del	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10 linkuse as main transcript	c.2135-5_2135-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015967.8	P1
	ENST00000664434.1 linkuse as main transcript	n.419-2041_419-2040del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000456

AC:

AN:

146968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000750

Gnomad ASJ

AF:

0.000583

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00186

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000331

Gnomad OTH

AF:

0.00148

GnomAD4 exome

AF:

0.0243

AC:

25843

AN:

1063444

Hom.:

AF XY:

0.0247

AC XY:

13188

AN XY:

533856

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0294

Gnomad4 EAS exome

AF:

0.00283

Gnomad4 SAS exome

AF:

0.0462

Gnomad4 FIN exome

AF:

0.0167

Gnomad4 NFE exome

AF:

0.0240

Gnomad4 OTH exome

AF:

0.0237

GnomAD4 genome

AF:

0.000456

AC:

AN:

147050

Hom.:

Cov.:

AF XY:

0.000434

AC XY:

AN XY:

71478

show subpopulations

Gnomad4 AFR

AF:

0.000297

Gnomad4 AMR

AF:

0.000750

Gnomad4 ASJ

AF:

0.000583

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00186

Gnomad4 NFE

AF:

0.000331

Gnomad4 OTH

AF:

0.00146

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over