1-198663227-C-T

Position:

• chr1-198663227-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000442510.8(PTPRC):​c.73+23886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,054 control chromosomes in the GnomAD database, including 10,044 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 0.35 (10044 hom., cov: 32)
• Consequence: PTPRC ENST00000442510.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.73+23886C>T		intron_variant		ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.73+23886C>T		intron_variant		1	NM_002838.5	ENSP00000411355	A2
	ENST00000566394.1	n.64-2521G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53630 AN: 151936 Hom.: 10033 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.353 AC: 53660 AN: 152054 Hom.: 10044 Cov.: 32 AF XY: 0.358 AC XY: 26638 AN XY: 74336

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.384

Alfa AF: 0.350 Hom.: 10094

Bravo AF: 0.349

Asia WGS AF: 0.573 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.68

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: rs1998843; hg19: chr1-198632356;