1-198665496-T-C

Variant names:

• chr1-198665496-T-C
• rs1052238
• NM_002838.5:c.73+26155T>C

Variant summary

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

The NM_002838.5(PTPRC):​c.73+26155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,752 control chromosomes in the GnomAD database, including 19,758 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 0.50 (19758 hom., cov: 30)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27
• Publications: 15 publications found

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]

PTPRC Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• T-B+ severe combined immunodeficiency due to CD45 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000261573 (HGNC:40483):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.73+26155T>C		intron_variant	Intron 2 of 32	ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.73+26155T>C		intron_variant	Intron 2 of 32	1	NM_002838.5	ENSP00000411355.3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76519 AN: 151634 Hom.: 19743 Cov.: 30

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.505 AC: 76564 AN: 151752 Hom.: 19758 Cov.: 30 AF XY: 0.505 AC XY: 37471 AN XY: 74142

African (AFR) AF: 0.440 AC: 18198 AN: 41340

American (AMR) AF: 0.516 AC: 7868 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3464

East Asian (EAS) AF: 0.679 AC: 3495 AN: 5144

South Asian (SAS) AF: 0.484 AC: 2331 AN: 4818

European-Finnish (FIN) AF: 0.559 AC: 5876 AN: 10506

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35352 AN: 67920

Other (OTH) AF: 0.533 AC: 1121 AN: 2104

Alfa AF: 0.521 Hom.: 69094

Bravo AF: 0.502

Asia WGS AF: 0.601 AC: 2091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0030
DANN	Benign	0.34
PhyloP100		-3.3
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: rs1052238; hg19: chr1-198634625;