rs3789184

Positions:

• chr5-170252033-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000524171.5(C5orf58):​c.*378A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 196,302 control chromosomes in the GnomAD database, including 24,181 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 0.49 (18658 hom., cov: 33)
  • Exomes 𝑓: 0.49 (5523 hom.)
• Consequence: C5orf58 ENST00000524171.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP2	NM_005565.5	c.1323+401T>C		intron_variant		ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.1092+401T>C		intron_variant			XP_047273127.1
C5orf58	NR_131091.3	n.587A>G		non_coding_transcript_exon_variant	4/4
C5orf58	NR_131092.3	n.503A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5orf58	ENST00000524171.5	c.*378A>G		3_prime_UTR_variant	4/4	1		ENSP00000490552.1
LCP2	ENST00000046794.10	c.1323+401T>C		intron_variant		1	NM_005565.5	ENSP00000046794.5
C5orf58	ENST00000517575.4	c.*378A>G		3_prime_UTR_variant	3/3	3		ENSP00000490661.1
LCP2	ENST00000521416.5	c.708+401T>C		intron_variant		2		ENSP00000428871.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74917 AN: 151948 Hom.: 18637 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.488 AC: 21589 AN: 44236 Hom.: 5523 Cov.: 0 AF XY: 0.489 AC XY: 11648 AN XY: 23812

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.493 AC: 74990 AN: 152066 Hom.: 18658 Cov.: 33 AF XY: 0.488 AC XY: 36262 AN XY: 74326

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.502

Alfa AF: 0.519 Hom.: 9303

Bravo AF: 0.499

Asia WGS AF: 0.529 AC: 1841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.32

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: rs3789184; hg19: chr5-169679037;