chr1-198638880-T-A

Position:

• chr1-198638880-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000643513.1(PTPRC):​c.-44+94T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 205,828 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (20 hom., cov: 32)
  • Exomes 𝑓: 0.011 (8 hom.)
• Consequence: PTPRC ENST00000643513.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.903

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=-0.79).
• BP6: Variant 1-198638880-T-A is Benign according to our data. Variant chr1-198638880-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1201379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.011 (1673/152256) while in subpopulation NFE AF= 0.0167 (1137/67976). AF 95% confidence interval is 0.0159. There are 20 homozygotes in gnomad4. There are 772 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRC	XM_047426381.1	c.-44+94T>A		intron_variant			XP_047282337.1
PTPRC	XM_047426398.1	c.-44+94T>A		intron_variant			XP_047282354.1
PTPRC	XM_047426409.1	c.-44+94T>A		intron_variant			XP_047282365.1
PTPRC	XM_047426415.1	c.-44+94T>A		intron_variant			XP_047282371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000367379.6	c.-44+182T>A		intron_variant		5		ENSP00000356349
PTPRC	ENST00000643513.1	c.-44+94T>A		intron_variant				ENSP00000494132

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1672 AN: 152138 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0115 AC: 616 AN: 53572 Hom.: 8 Cov.: 0 AF XY: 0.0105 AC XY: 304 AN XY: 28846

Gnomad4 AFR exome AF: 0.00235

Gnomad4 AMR exome AF: 0.00780

Gnomad4 ASJ exome AF: 0.0502

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00293

Gnomad4 FIN exome AF: 0.00326

Gnomad4 NFE exome AF: 0.0146

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0110 AC: 1673 AN: 152256 Hom.: 20 Cov.: 32 AF XY: 0.0104 AC XY: 772 AN XY: 74450

Gnomad4 AFR AF: 0.00286

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0150 Hom.: 5

Bravo AF: 0.0103

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75725159; hg19: chr1-198608010;