rs31517

chr5-135951340-T-Cchr5-135951340-T-G

Variant summary

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

The NM_002302.3(LECT2):c.172A>G(p.Ile58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,612,554 control chromosomes in the GnomAD database, including 320,989 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.62 (29324 hom., cov: 32)
  • Exomes 𝑓: 0.63 (291665 hom.)
• Consequence: LECT2 NM_002302.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.496

Genes affected

LECT2 (HGNC:6550): (leukocyte cell derived chemotaxin 2) This gene encodes a secreted, 16 kDa protein that acts as a chemotactic factor to neutrophils and stimulates the growth of chondrocytes and osteoblasts. This protein has high sequence similarity to the chondromodulin repeat regions of the chicken myb-induced myeloid 1 protein. A polymorphism in this gene may be associated with rheumatoid arthritis. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0176246E-6).
• BP6: Variant 5-135951340-T-C is Benign according to our data. Variant chr5-135951340-T-C is described in ClinVar as [Benign]. Clinvar id is 3060729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LECT2	NM_002302.3	c.172A>G	p.Ile58Val	missense_variant	3/4	ENST00000274507.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LECT2	ENST00000274507.6	c.172A>G	p.Ile58Val	missense_variant	3/4	1	NM_002302.3	P1
	ENST00000467490.5	n.1491T>C		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94004 AN: 151920 Hom.: 29301 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.607

GnomAD3 exomes AF: 0.645 AC: 161816 AN: 251034 Hom.: 52372 AF XY: 0.645 AC XY: 87525 AN XY: 135636

Gnomad AFR exome AF: 0.569

Gnomad AMR exome AF: 0.701

Gnomad ASJ exome AF: 0.590

Gnomad EAS exome AF: 0.645

Gnomad SAS exome AF: 0.676

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.632

Gnomad OTH exome AF: 0.625

GnomAD4 exome AF: 0.631 AC: 921347 AN: 1460516 Hom.: 291665 Cov.: 39 AF XY: 0.632 AC XY: 459492 AN XY: 726604

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.624

GnomAD4 genome AF: 0.619 AC: 94062 AN: 152038 Hom.: 29324 Cov.: 32 AF XY: 0.622 AC XY: 46185 AN XY: 74310

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.611

Alfa AF: 0.624 Hom.: 75811

Bravo AF: 0.614

TwinsUK AF: 0.610 AC: 2261

ALSPAC AF: 0.630 AC: 2429

ESP6500AA AF: 0.579 AC: 2550

ESP6500EA AF: 0.636 AC: 5472

ExAC AF: 0.644 AC: 78237

Asia WGS AF: 0.673 AC: 2338 AN: 3478

EpiCase AF: 0.628

EpiControl AF: 0.636

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

LECT2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.6
Dann	Benign	0.62
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.50	T;T;T
MetaRNN	Benign	0.0000010	T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.11	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.53	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.025
MPC		0.023
ClinPred		0.0013	T
GERP RS		3.3
Varity_R		0.023
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs31517; hg19: chr5-135287029; COSMIC: COSV50846723;