rs1326269

Variant names:

• chr1-198644825-T-A
• rs1326269
• NM_002838.5:c.73+5484T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-198644825-T-A
• chr1-198644825-T-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+5484T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,450 control chromosomes in the GnomAD database, including 19,180 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 0.49 (19180 hom., cov: 31)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.73+5484T>A		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+5484T>A		intron_variant	Intron 2 of 32	1	NM_002838.5	ENSP00000411355.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74348 AN: 151332 Hom.: 19155 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.491 AC: 74431 AN: 151450 Hom.: 19180 Cov.: 31 AF XY: 0.499 AC XY: 36897 AN XY: 74002

African (AFR) AF: 0.580 AC: 23951 AN: 41326

American (AMR) AF: 0.519 AC: 7870 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1413 AN: 3458

East Asian (EAS) AF: 0.816 AC: 4198 AN: 5144

South Asian (SAS) AF: 0.573 AC: 2754 AN: 4810

European-Finnish (FIN) AF: 0.485 AC: 5110 AN: 10544

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27546 AN: 67688

Other (OTH) AF: 0.488 AC: 1025 AN: 2102

Alfa AF: 0.464 Hom.: 2073

Bravo AF: 0.498

Asia WGS AF: 0.706 AC: 2447 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.61
PhyloP100		0.31
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: rs1326269; hg19: chr1-198613955;