1-198694217-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000413409.6(PTPRC):c.*36G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,395,476 control chromosomes in the GnomAD database, including 2,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (275 hom., cov: 31)
  • Exomes 𝑓: 0.062 (2580 hom.)
• Consequence: PTPRC ENST00000413409.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.508

Genes affected

PTPRC (HGNC:9666): (protein tyrosine phosphatase receptor type C) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitosis, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus is classified as a receptor type PTP. This PTP has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes, or by activating various Src family kinases required for the antigen receptor signaling. This PTP also suppresses JAK kinases, and thus functions as a regulator of cytokine receptor signaling. Alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-198694217-G-A is Benign according to our data. Variant chr1-198694217-G-A is described in ClinVar as [Benign]. Clinvar id is 1277649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRC	NM_002838.5	c.100+1844G>A		intron_variant		ENST00000442510.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRC	ENST00000442510.8	c.100+1844G>A		intron_variant		1	NM_002838.5	A2

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7020 AN: 151628 Hom.: 275 Cov.: 31

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.0359

GnomAD3 exomes AF: 0.0534 AC: 2798 AN: 52352 Hom.: 103 AF XY: 0.0554 AC XY: 1545 AN XY: 27872

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0178

Gnomad ASJ exome AF: 0.0263

Gnomad EAS exome AF: 0.000633

Gnomad SAS exome AF: 0.0362

Gnomad FIN exome AF: 0.0938

Gnomad NFE exome AF: 0.0642

Gnomad OTH exome AF: 0.0374

GnomAD4 exome AF: 0.0616 AC: 76607 AN: 1243730 Hom.: 2580 Cov.: 21 AF XY: 0.0612 AC XY: 37068 AN XY: 605920

Gnomad4 AFR exome AF: 0.00894

Gnomad4 AMR exome AF: 0.0176

Gnomad4 ASJ exome AF: 0.0303

Gnomad4 EAS exome AF: 0.000310

Gnomad4 SAS exome AF: 0.0366

Gnomad4 FIN exome AF: 0.0955

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.0494

GnomAD4 genome AF: 0.0462 AC: 7016 AN: 151746 Hom.: 275 Cov.: 31 AF XY: 0.0463 AC XY: 3428 AN XY: 74108

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0260

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.0337

Gnomad4 FIN AF: 0.0982

Gnomad4 NFE AF: 0.0695

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0564 Hom.: 73

Bravo AF: 0.0376

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.51
Dann	Benign	0.72

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: rs78958674; hg19: chr1-198663346;