rs1885177

Variant names:

• chr20-50574691-A-C
• rs1885177
• NM_002827.4:c.492+37A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-50574691-A-C
• chr20-50574691-A-G
• chr20-50574691-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002827.4(PTPN1):​c.492+37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,564,756 control chromosomes in the GnomAD database, including 213,858 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 0.47 (17640 hom., cov: 33)
  • Exomes 𝑓: 0.52 (196218 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 16 publications found

Genes affected

PTPN1 (HGNC:9642): (protein tyrosine phosphatase non-receptor type 1) The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

PTPN1 Gene-Disease associations (from GenCC):

• autoinflammatory syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000232043 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.492+37A>C		intron_variant	Intron 5 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.273+37A>C		intron_variant	Intron 4 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.492+37A>C		intron_variant	Intron 5 of 9	1	NM_002827.4	ENSP00000360683.3
ENSG00000232043	ENST00000431019.1	n.871T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
PTPN1	ENST00000541713.5	c.273+37A>C		intron_variant	Intron 4 of 8	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72064 AN: 151972 Hom.: 17640 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.504

GnomAD2 exomes AF: 0.529 AC: 109113 AN: 206354 AF XY: 0.536

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.526

Gnomad EAS exome AF: 0.619

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.518

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.524 AC: 740865 AN: 1412666 Hom.: 196218 Cov.: 34 AF XY: 0.528 AC XY: 370836 AN XY: 702978

African (AFR) AF: 0.326 AC: 9801 AN: 30084

American (AMR) AF: 0.514 AC: 16745 AN: 32590

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 12990 AN: 24764

East Asian (EAS) AF: 0.642 AC: 23657 AN: 36876

South Asian (SAS) AF: 0.627 AC: 48854 AN: 77900

European-Finnish (FIN) AF: 0.544 AC: 28880 AN: 53098

Middle Eastern (MID) AF: 0.586 AC: 3318 AN: 5664

European-Non Finnish (NFE) AF: 0.518 AC: 565833 AN: 1093188

Other (OTH) AF: 0.526 AC: 30787 AN: 58502

GnomAD4 genome AF: 0.474 AC: 72083 AN: 152090 Hom.: 17640 Cov.: 33 AF XY: 0.477 AC XY: 35449 AN XY: 74348

African (AFR) AF: 0.334 AC: 13837 AN: 41488

American (AMR) AF: 0.504 AC: 7694 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3253 AN: 5158

South Asian (SAS) AF: 0.617 AC: 2976 AN: 4822

European-Finnish (FIN) AF: 0.540 AC: 5712 AN: 10574

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34965 AN: 67982

Other (OTH) AF: 0.507 AC: 1071 AN: 2114

Alfa AF: 0.418 Hom.: 2480

Bravo AF: 0.466

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.035
DANN	Benign	0.61
PhyloP100		-1.3
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: rs1885177; hg19: chr20-49191228; COSMIC: COSV65409181;