5-170252350-C-T

Variant names:

• chr5-170252350-C-T
• rs1546451
• ENST00000524171.5:c.*695C>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 rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.1323+84G>A		intron_variant	Intron 19 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.1092+84G>A		intron_variant	Intron 17 of 18		XP_047273127.1
C5orf58	NR_131091.3	n.904C>T		non_coding_transcript_exon_variant	Exon 4 of 4
C5orf58	NR_131092.3	n.820C>T		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5orf58	ENST00000524171.5	c.*695C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000490552.1
LCP2	ENST00000046794.10	c.1323+84G>A		intron_variant	Intron 19 of 20	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.708+84G>A		intron_variant	Intron 11 of 12	2		ENSP00000428871.1
C5orf58	ENST00000517575.4	c.*695C>T		downstream_gene_variant		3		ENSP00000490661.1

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;