1-198743340-T-G

Variant names:

• chr1-198743340-T-G
• rs1932435
• NM_002838.5:c.2698-714T>G

Variant summary

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

The NM_002838.5(PTPRC):​c.2698-714T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,746 control chromosomes in the GnomAD database, including 3,152 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 0.19 (3152 hom., cov: 32)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 10 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]

MIR181A1HG (HGNC:48659): (MIR181A1 host gene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.2698-714T>G		intron_variant	Intron 25 of 32	ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.2698-714T>G		intron_variant	Intron 25 of 32	1	NM_002838.5	ENSP00000411355.3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28096 AN: 151628 Hom.: 3143 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.185 AC: 28133 AN: 151746 Hom.: 3152 Cov.: 32 AF XY: 0.183 AC XY: 13564 AN XY: 74136

African (AFR) AF: 0.295 AC: 12200 AN: 41422

American (AMR) AF: 0.227 AC: 3448 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1318 AN: 5126

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4816

European-Finnish (FIN) AF: 0.0675 AC: 714 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8579 AN: 67814

Other (OTH) AF: 0.174 AC: 367 AN: 2104

Alfa AF: 0.128 Hom.: 788

Bravo AF: 0.203

Asia WGS AF: 0.239 AC: 829 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.50
PhyloP100		0.57
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: rs1932435; hg19: chr1-198712469;