19-54663551-G-T

Variant names:

• chr19-54663551-G-T
• rs11540761
• NM_001278426.4:c.54G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2850 hom., cov: 31)
  • Exomes 𝑓: 0.19 (27870 hom.)
• Consequence: LILRB4 NM_001278426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.54G>T	p.Arg18Ser	missense_variant	Exon 2 of 12	ENST00000695418.1	NP_001265355.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29393 AN: 151730 Hom.: 2850 Cov.: 31

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

GnomAD2 exomes AF: 0.196 AC: 49269 AN: 251294 AF XY: 0.201

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 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.: 68 AF XY: 0.196 AC XY: 142146 AN XY: 726866

African (AFR) AF: 0.211 AC: 7053 AN: 33454

American (AMR) AF: 0.202 AC: 9054 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 5782 AN: 26134

East Asian (EAS) AF: 0.130 AC: 5149 AN: 39700

South Asian (SAS) AF: 0.293 AC: 25250 AN: 86238

European-Finnish (FIN) AF: 0.170 AC: 9075 AN: 53414

Middle Eastern (MID) AF: 0.198 AC: 1062 AN: 5368

European-Non Finnish (NFE) AF: 0.185 AC: 206184 AN: 1111758

Other (OTH) AF: 0.193 AC: 11637 AN: 60332

GnomAD4 genome AF: 0.194 AC: 29403 AN: 151846 Hom.: 2850 Cov.: 31 AF XY: 0.195 AC XY: 14438 AN XY: 74198

African (AFR) AF: 0.207 AC: 8559 AN: 41380

American (AMR) AF: 0.192 AC: 2927 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3470

East Asian (EAS) AF: 0.123 AC: 636 AN: 5168

South Asian (SAS) AF: 0.287 AC: 1379 AN: 4810

European-Finnish (FIN) AF: 0.172 AC: 1810 AN: 10504

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 290

European-Non Finnish (NFE) AF: 0.187 AC: 12696 AN: 67926

Other (OTH) AF: 0.192 AC: 405 AN: 2114

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	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.0	.;.;T;.;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.80	T;.;T;T;T;T
MetaRNN	Benign	0.0056	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	.;.;.;.;.;.
PhyloP100		0.28
PrimateAI	Benign	0.23	T
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
Vest4		0.0
ClinPred		0.030	T
GERP RS		1.3
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11540761; hg19: chr19-55175009; COSMIC: COSV54404480; COSMIC: COSV54404480;