rs2359952

chr1-198687278-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002838.5(PTPRC):c.74-5069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,892 control chromosomes in the GnomAD database, including 11,009 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 0.37 (11009 hom., cov: 31)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRC	NM_002838.5	c.74-5069A>G		intron_variant		ENST00000442510.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRC	ENST00000442510.8	c.74-5069A>G		intron_variant		1	NM_002838.5	A2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56534 AN: 151774 Hom.: 10988 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.340

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56588 AN: 151892 Hom.: 11009 Cov.: 31 AF XY: 0.374 AC XY: 27759 AN XY: 74230

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.340

Alfa AF: 0.326 Hom.: 14702

Bravo AF: 0.390

Asia WGS AF: 0.434 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.11
Dann	Benign	0.25

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: rs2359952; hg19: chr1-198656407;