rs3764147

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I254M) has been classified as Uncertain significance.

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

Publications

167 publications found

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 Gene-Disease associations (from GenCC):

juvenile arthritis due to defect in LACC1
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LACC1 links:

ENSG00000281883 (HGNC:):

ENSG00000281883 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
LACC1	NM_153218.4 link	c.760A>G	p.Ile254Val	missense_variant	Exon 4 of 7	ENST00000325686.7	NP_694950.2	Q8IV20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LACC1	ENST00000325686.7 link	c.760A>G	p.Ile254Val	missense_variant	Exon 4 of 7	1	NM_153218.4	ENSP00000317619.5	Q8IV20
LACC1	ENST00000441843.5 link	c.760A>G	p.Ile254Val	missense_variant	Exon 4 of 7	5		ENSP00000391747.1	Q8IV20
ENSG00000281883	ENST00000627615.1 link	n.-12A>G		upstream_gene_variant		5		ENSP00000486083.1	A0A0D9SEW6

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

GnomAD2 exomes

AF:

0.277

AC:

69444

AN:

250572

AF XY:

0.274

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 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

African (AFR)

AF:

0.311

AC:

10372

AN:

33356

American (AMR)

AF:

0.383

AC:

17014

AN:

44476

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

10392

AN:

26042

East Asian (EAS)

AF:

0.320

AC:

12678

AN:

39638

South Asian (SAS)

AF:

0.296

AC:

25460

AN:

85908

European-Finnish (FIN)

AF:

0.205

AC:

10931

AN:

53332

Middle Eastern (MID)

AF:

0.281

AC:

1619

AN:

5756

European-Non Finnish (NFE)

AF:

0.217

AC:

240702

AN:

1109180

Other (OTH)

AF:

0.241

AC:

14544

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

11089

22178

33268

44357

55446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8408

16816

25224

33632

42040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.269

AC:

40850

AN:

152048

Hom.:

5714

Cov.:

AF XY:

0.271

AC XY:

20149

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.309

AC:

12803

AN:

41458

American (AMR)

AF:

0.326

AC:

4974

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1387

AN:

3468

East Asian (EAS)

AF:

0.318

AC:

1642

AN:

5164

South Asian (SAS)

AF:

0.297

AC:

1431

AN:

4816

European-Finnish (FIN)

AF:

0.207

AC:

2191

AN:

10574

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15678

AN:

67968

Other (OTH)

AF:

0.258

AC:

546

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1480

2959

4439

5918

7398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.248

Hom.:

24622

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Juvenile arthritis due to defect in LACC1

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Leprosy, susceptibility to, 1

Other:1

Jun 10, 2022

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

Significance:Uncertain risk allele

Review Status:no assertion criteria provided

Collection Method:case-control

- -

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

(source)

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

PhyloP100

2.7

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over