chr5-170252350-C-T

Variant names:

• chr5-170252350-C-T
• rs1546451
• ENST00000524171.5:c.*695C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

LCP2 Gene-Disease associations (from GenCC):

• immunodeficiency 81

  Inheritance: AR, Unknown Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524171.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	NM_005565.5	MANE Select	c.1323+84G>A		intron	N/A	NP_005556.1	Q13094
	C5orf58	NR_131091.3		n.904C>T		non_coding_transcript_exon	Exon 4 of 4
	C5orf58	NR_131092.3		n.820C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5orf58	ENST00000524171.5	TSL:1	c.*695C>T		3_prime_UTR	Exon 4 of 4	ENSP00000490552.1	A0A1B0GVU6
	LCP2	ENST00000046794.10	TSL:1 MANE Select	c.1323+84G>A		intron	N/A	ENSP00000046794.5	Q13094
	LCP2	ENST00000968849.1		c.1332+84G>A		intron	N/A	ENSP00000638908.1

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

African (AFR) AF: 0.268 AC: 3975 AN: 14826

American (AMR) AF: 0.460 AC: 11281 AN: 24542

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 8337 AN: 17174

East Asian (EAS) AF: 0.415 AC: 13012 AN: 31350

South Asian (SAS) AF: 0.533 AC: 28096 AN: 52700

European-Finnish (FIN) AF: 0.429 AC: 16960 AN: 39570

Middle Eastern (MID) AF: 0.458 AC: 1764 AN: 3850

European-Non Finnish (NFE) AF: 0.519 AC: 190796 AN: 367950

Other (OTH) AF: 0.483 AC: 14367 AN: 29724

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

African (AFR) AF: 0.274 AC: 11365 AN: 41448

American (AMR) AF: 0.460 AC: 7026 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2062 AN: 5156

South Asian (SAS) AF: 0.534 AC: 2575 AN: 4824

European-Finnish (FIN) AF: 0.412 AC: 4338 AN: 10536

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35171 AN: 67980

Other (OTH) AF: 0.458 AC: 966 AN: 2110

Alfa AF: 0.463 Hom.: 3341

Bravo AF: 0.430

Asia WGS AF: 0.490 AC: 1706 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.34
PhyloP100		1.4
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: rs1546451; hg19: chr5-169679354; COSMIC: COSV50452222; COSMIC: COSV50452222;