chr1-198696518-T-C

Variant names:

• chr1-198696518-T-C
• rs12120474
• NM_002838.5:c.101-194T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002838.5(PTPRC):​c.101-194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 152,284 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (22 hom., cov: 32)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.434
• Publications: 0 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-198696518-T-C is Benign according to our data. Variant chr1-198696518-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0129 (1972/152284) while in subpopulation NFE AF = 0.0161 (1093/68018). AF 95% confidence interval is 0.0153. There are 22 homozygotes in GnomAd4. There are 1052 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.101-194T>C		intron_variant	Intron 3 of 32	ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.101-194T>C		intron_variant	Intron 3 of 32	1	NM_002838.5	ENSP00000411355.3

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1971 AN: 152166 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0129 AC: 1972 AN: 152284 Hom.: 22 Cov.: 32 AF XY: 0.0141 AC XY: 1052 AN XY: 74468

African (AFR) AF: 0.00231 AC: 96 AN: 41570

American (AMR) AF: 0.0103 AC: 158 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 21 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4822

European-Finnish (FIN) AF: 0.0488 AC: 518 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0161 AC: 1093 AN: 68018

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.0150 Hom.: 0

Bravo AF: 0.00935

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 05, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.44
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism

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: rs12120474; hg19: chr1-198665647;