rs3764147

Positions:

chr13-43883789-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153218.4(LACC1):c.760A>G(p.Ile254Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,609,972 control chromosomes in the GnomAD database, including 48,467 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.27 ( 5714 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42753 hom. )

Consequence

LACC1
NM_153218.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

LACC1 (HGNC:26789): (laccase domain containing 1) This gene encodes an oxidoreductase that promotes fatty-acid oxidation, with concomitant inflammasome activation, mitochondrial and NADPH-oxidase-dependent reactive oxygen species production, and bactericidal activity of macrophages. The encoded protein forms a complex with fatty acid synthase on peroxisomes and is thought to be modulated by peroxisome proliferator-activated receptor signaling events. Naturally occurring mutations in this gene are associated with inflammatory bowel disease, Behcet's disease, leprosy, ulcerative colitis, early-onset Crohn's disease, and systemic juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

LACC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043236315).

BP6

Variant 13-43883789-A-G is Benign according to our data. Variant chr13-43883789-A-G is described in ClinVar as [Benign]. Clinvar id is 1300105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACC1	NM_153218.4 linkuse as main transcript	c.760A>G	p.Ile254Val	missense_variant	4/7	ENST00000325686.7	NP_694950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACC1	ENST00000325686.7 linkuse as main transcript	c.760A>G	p.Ile254Val	missense_variant	4/7	1	NM_153218.4	ENSP00000317619	P1
LACC1	ENST00000441843.5 linkuse as main transcript	c.760A>G	p.Ile254Val	missense_variant	4/7	5		ENSP00000391747	P1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40822

AN:

151930

Hom.:

5706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.277

AC:

69444

AN:

250572

Hom.:

10215

AF XY:

0.274

AC XY:

37066

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.311

Gnomad SAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.236

AC:

343712

AN:

1457924

Hom.:

42753

Cov.:

AF XY:

0.238

AC XY:

172651

AN XY:

725398

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.399

Gnomad4 EAS exome

AF:

0.320

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.269

AC:

40850

AN:

152048

Hom.:

5714

Cov.:

AF XY:

0.271

AC XY:

20149

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.231

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.248

Hom.:

12724

Bravo

AF:

0.279

TwinsUK

AF:

0.214

AC:

792

ALSPAC

AF:

0.221

AC:

851

ESP6500AA

AF:

0.294

AC:

1297

ESP6500EA

AF:

0.230

AC:

1981

ExAC

AF:

0.270

AC:

32755

Asia WGS

AF:

0.257

AC:

889

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Juvenile arthritis due to defect in LACC1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Leprosy, susceptibility to, 1

Other:1

Uncertain risk allele, no assertion criteria provided

case-control

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Jun 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.80

DANN

Benign

0.84

DEOGEN2

Benign

0.0048

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.54

T;.

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.5

N;N

MutationTaster

Benign

0.97

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

0.43

N;N

REVEL

Benign

0.036

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.023

MPC

0.28

ClinPred

0.00037

GERP RS

1.9

Varity_R

0.034

gMVP

0.65

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over