rs10919563

Positions:

• chr1-198731313-G-A
• chr1-198731313-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002838.5(PTPRC):​c.1865-304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,850 control chromosomes in the GnomAD database, including 4,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4464 hom., cov: 32)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-198731313-G-A is Benign according to our data. Variant chr1-198731313-G-A is described in ClinVar as [Benign]. Clinvar id is 1261380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.1865-304G>A		intron_variant		ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.1865-304G>A		intron_variant		1	NM_002838.5	ENSP00000411355	A2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31955 AN: 151734 Hom.: 4448 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.211 AC: 32012 AN: 151850 Hom.: 4464 Cov.: 32 AF XY: 0.207 AC XY: 15383 AN XY: 74236

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.191

Alfa AF: 0.172 Hom.: 765

Bravo AF: 0.232

Asia WGS AF: 0.236 AC: 819 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10919563; hg19: chr1-198700442;