Genetic Variant LILRB4:p.Arg18Ser (chr19-54663551-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001278426.4(LILRB4):c.54G>T(p.Arg18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,612,964 control chromosomes in the GnomAD database, including 30,720 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2850 hom., cov: 31)

Exomes 𝑓: 0.19 ( 27870 hom. )

Consequence

LILRB4
NM_001278426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.280

Variant links:

Genes affected

LILRB4 (HGNC:6608): (leukocyte immunoglobulin like receptor B4) This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. The receptor can also function in antigen capture and presentation. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

LILRB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005641222).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB4	NM_001278426.4 link	c.54G>T	p.Arg18Ser	missense_variant	Exon 2 of 12	ENST00000695418.1	NP_001265355.2	Q8NHJ6A0A8Q3SHR1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1 link	c.54G>T	p.Arg18Ser	missense_variant	Exon 2 of 12		NM_001278426.4	ENSP00000511897.1		A0A8Q3SHR1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29393

AN:

151730

Hom.:

2850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.196

AC:

49269

AN:

251294

Hom.:

5031

AF XY:

0.201

AC XY:

27287

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.192

AC:

280246

AN:

1461118

Hom.:

27870

Cov.:

AF XY:

0.196

AC XY:

142146

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.221

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.194

AC:

29403

AN:

151846

Hom.:

2850

Cov.:

AF XY:

0.195

AC XY:

14438

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.193

Hom.:

1223

Bravo

AF:

0.195

TwinsUK

AF:

0.183

AC:

678

ALSPAC

AF:

0.180

AC:

693

ESP6500AA

AF:

0.217

AC:

957

ESP6500EA

AF:

0.186

AC:

1598

ExAC

AF:

0.197

AC:

23963

Asia WGS

AF:

0.211

AC:

732

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.072

.;.;T;.;T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.80

T;.;T;T;T;T

MetaRNN

Benign

0.0056

T;T;T;T;T;T

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.5

D;D;D;D;D;D

REVEL

Benign

0.11

Sift

Benign

0.41

T;D;T;T;D;D

Sift4G

Benign

0.075

T;T;D;T;T;T

Polyphen

0.40

.;.;.;.;.;B

Vest4

0.11, 0.11, 0.21, 0.10

MutPred

0.43

.;Loss of methylation at R18 (P = 0.0171);Loss of methylation at R18 (P = 0.0171);Loss of methylation at R18 (P = 0.0171);Loss of methylation at R18 (P = 0.0171);Loss of methylation at R18 (P = 0.0171);

MPC

0.033

ClinPred

0.030

GERP RS

1.3

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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