5-135951340-T-C

Variant names:

• chr5-135951340-T-C
• rs31517
• NM_002302.3:c.172A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.62 (29324 hom., cov: 32)
  • Exomes 𝑓: 0.63 (291665 hom.)
• Consequence: LECT2 NM_002302.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.496
• Publications: 53 publications found

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]

ENSG00000293402 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 3060729.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002302.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LECT2	NM_002302.3	MANE Select	c.172A>G	p.Ile58Val	missense	Exon 3 of 4	NP_002293.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LECT2	ENST00000274507.6	TSL:1 MANE Select	c.172A>G	p.Ile58Val	missense	Exon 3 of 4	ENSP00000274507.1
	ENSG00000293402	ENST00000467490.5	TSL:1	n.1491T>C		non_coding_transcript_exon	Exon 7 of 7
	LECT2	ENST00000522943.5	TSL:3	c.172A>G	p.Ile58Val	missense	Exon 3 of 4	ENSP00000429618.1

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

GnomAD2 exomes AF: 0.645 AC: 161816 AN: 251034 AF XY: 0.645

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 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

African (AFR) AF: 0.565 AC: 18925 AN: 33468

American (AMR) AF: 0.694 AC: 31032 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 15326 AN: 26124

East Asian (EAS) AF: 0.610 AC: 24209 AN: 39682

South Asian (SAS) AF: 0.678 AC: 58419 AN: 86154

European-Finnish (FIN) AF: 0.662 AC: 35345 AN: 53406

Middle Eastern (MID) AF: 0.622 AC: 3579 AN: 5758

European-Non Finnish (NFE) AF: 0.627 AC: 696871 AN: 1110864

Other (OTH) AF: 0.624 AC: 37641 AN: 60342

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

African (AFR) AF: 0.573 AC: 23756 AN: 41468

American (AMR) AF: 0.661 AC: 10096 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2052 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3303 AN: 5152

South Asian (SAS) AF: 0.689 AC: 3316 AN: 4812

European-Finnish (FIN) AF: 0.660 AC: 6965 AN: 10560

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42480 AN: 67988

Other (OTH) AF: 0.611 AC: 1291 AN: 2114

Alfa AF: 0.622 Hom.: 102243

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	LECT2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.50
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.14
Sift	Benign	0.53	T
Sift4G	Benign	1.0	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
Mutation Taster		=294/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs31517; hg19: chr5-135287029; COSMIC: COSV50846723;