Variant 14-92732735-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005606.7(LGMN):c.52G>A(p.Val18Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,613,640 control chromosomes in the GnomAD database, including 28,202 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 3702 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24500 hom. )

Consequence

LGMN
NM_005606.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

Variant links:

Genes affected

LGMN (HGNC:9472): (legumain) This gene encodes a cysteine protease that has a strict specificity for hydrolysis of asparaginyl bonds. This enzyme may be involved in the processing of bacterial peptides and endogenous proteins for MHC class II presentation in the lysosomal/endosomal systems. Enzyme activation is triggered by acidic pH and appears to be autocatalytic. Protein expression occurs after monocytes differentiate into dendritic cells. A fully mature, active enzyme is produced following lipopolysaccharide expression in mature dendritic cells. Overexpression of this gene may be associated with the majority of solid tumor types. This gene has a pseudogene on chromosome 13. Several alternatively spliced transcript variants have been described, but the biological validity of only two has been determined. These two variants encode the same isoform. [provided by RefSeq, Jul 2008]

LGMN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004764706).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGMN	NM_005606.7 linkuse as main transcript	c.52G>A	p.Val18Ile	missense_variant	2/14	ENST00000334869.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGMN	ENST00000334869.9 linkuse as main transcript	c.52G>A	p.Val18Ile	missense_variant	2/14	1	NM_005606.7	P1	Q99538-1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32525

AN:

151976

Hom.:

3694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.198

AC:

49732

AN:

251330

Hom.:

5317

AF XY:

0.191

AC XY:

25966

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.292

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.179

AC:

262231

AN:

1461546

Hom.:

24500

Cov.:

AF XY:

0.178

AC XY:

129743

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.214

AC:

32550

AN:

152094

Hom.:

3702

Cov.:

AF XY:

0.216

AC XY:

16025

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.186

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.183

Hom.:

4351

Bravo

AF:

0.223

TwinsUK

AF:

0.169

AC:

628

ALSPAC

AF:

0.181

AC:

698

ESP6500AA

AF:

0.296

AC:

1303

ESP6500EA

AF:

0.165

AC:

1418

ExAC

AF:

0.193

AC:

23478

Asia WGS

AF:

0.251

AC:

873

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.0030

DANN

Benign

0.69

DEOGEN2

Benign

0.099

.;T;.;T;T;T;T;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.54

T;.;T;T;T;.;T;.;T;.

MetaRNN

Benign

0.0048

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;L;L;.;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

0.070

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.054

Sift

Benign

0.33

T;T;T;T;T;T;T;T;T;.

Sift4G

Benign

0.38

T;T;T;T;T;.;.;.;.;.

Polyphen

0.0

.;B;.;B;.;.;.;.;.;.

Vest4

0.054

MPC

0.24

ClinPred

0.010

GERP RS

-9.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.017

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over