5-170252350-C-T

Variant summary

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

The ENST00000524171.5(C5orf58):c.*695C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 733,698 control chromosomes in the GnomAD database, including 88,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (15311 hom., cov: 32)
  • Exomes 𝑓: 0.50 (73048 hom.)
• Consequence: C5orf58 ENST00000524171.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45

Genes affected

C5orf58 (HGNC:37272): (chromosome 5 open reading frame 58)

LCP2 (HGNC:6529): (lymphocyte cytosolic protein 2) This gene encodes an adapter protein that acts as a substrate of the T cell antigen receptor (TCR)-activated protein tyrosine kinase pathway. The encoded protein associates with growth factor receptor bound protein 2, and is thought to play a role TCR-mediated intracellular signal transduction. A similar protein in mouse plays a role in normal T-cell development and activation. Mice lacking this gene show subcutaneous and intraperitoneal fetal hemorrhaging, dysfunctional platelets and impaired viability. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-170252350-C-T is Benign according to our data. Variant chr5-170252350-C-T is described in ClinVar as [Benign]. Clinvar id is 2688122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.1323+84G>A		intron_variant		ENST00000046794.10
LCP2	XM_047417171.1	c.1092+84G>A		intron_variant
C5orf58	NR_131091.3	n.904C>T		non_coding_transcript_exon_variant	4/4
C5orf58	NR_131092.3	n.820C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5orf58	ENST00000524171.5	c.*695C>T		3_prime_UTR_variant	4/4	1
LCP2	ENST00000046794.10	c.1323+84G>A		intron_variant		1	NM_005565.5	P1
LCP2	ENST00000521416.5	c.708+84G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65820 AN: 151894 Hom.: 15295 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.496 AC: 288588 AN: 581686 Hom.: 73048 Cov.: 8 AF XY: 0.499 AC XY: 153363 AN XY: 307148

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.433 AC: 65872 AN: 152012 Hom.: 15311 Cov.: 32 AF XY: 0.429 AC XY: 31914 AN XY: 74310

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.458

Alfa AF: 0.467 Hom.: 3310

Bravo AF: 0.430

Asia WGS AF: 0.490 AC: 1706 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.3
Dann	Benign	0.34

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: rs1546451; hg19: chr5-169679354; COSMIC: COSV50452222; COSMIC: COSV50452222;