rs3764147

chr13-43883789-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 2.74

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]

ACMG classification

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	UniProt
LACC1	NM_153218.4	c.760A>G	p.Ile254Val	missense_variant	4/7	ENST00000325686.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40822 AN: 151930 Hom.: 5706 Cov.: 32

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

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.: 31 AF XY: 0.238 AC XY: 172651 AN XY: 725398

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.: 32 AF XY: 0.271 AC XY: 20149 AN XY: 74328

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:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

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. -

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	T
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	N
LIST_S2	Benign	0.54	T;.
MetaRNN	Benign	0.0043	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.5	N;N
MutationTaster	Benign	0.97	P;P
PrimateAI	Benign	0.26	T
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	T
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

Other links and lift over

dbSNP: rs3764147; hg19: chr13-44457925; COSMIC: COSV57828643; COSMIC: COSV57828643;