1-198674995-C-T

Variant names:

• chr1-198674995-C-T
• rs9803750
• NM_002838.5:c.74-17352C>T

Variant summary

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

The NM_002838.5(PTPRC):​c.74-17352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,948 control chromosomes in the GnomAD database, including 13,879 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 0.40 (13879 hom., cov: 32)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002838.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	NM_002838.5	MANE Select	c.74-17352C>T		intron	N/A	NP_002829.3
	PTPRC	NM_080921.4		c.74-17352C>T		intron	N/A	NP_563578.2	P08575-4
	PTPRC	NM_001267798.2		c.74-17352C>T		intron	N/A	NP_001254727.1	M9MML4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.74-17352C>T		intron	N/A	ENSP00000411355.3	P08575-3
	PTPRC	ENST00000348564.12	TSL:1	c.74-17352C>T		intron	N/A	ENSP00000306782.7	P08575-4
	PTPRC	ENST00000530727.5	TSL:1	c.74-17352C>T		intron	N/A	ENSP00000433536.2	E9PKH0

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60589 AN: 151830 Hom.: 13837 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.399 AC: 60684 AN: 151948 Hom.: 13879 Cov.: 32 AF XY: 0.397 AC XY: 29464 AN XY: 74252

African (AFR) AF: 0.630 AC: 26098 AN: 41432

American (AMR) AF: 0.385 AC: 5875 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3470

East Asian (EAS) AF: 0.176 AC: 915 AN: 5186

South Asian (SAS) AF: 0.354 AC: 1710 AN: 4826

European-Finnish (FIN) AF: 0.277 AC: 2928 AN: 10554

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20790 AN: 67916

Other (OTH) AF: 0.351 AC: 738 AN: 2104

Alfa AF: 0.336 Hom.: 26746

Bravo AF: 0.418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.016
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: rs9803750; hg19: chr1-198644124;