19-54663046-T-C

Variant names:

• chr19-54663046-T-C
• rs28366008
• NM_001278426.4:c.13T>C

Variant summary

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

The NM_001278426.4(LILRB4):​c.13T>C​(p.Phe5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,613,290 control chromosomes in the GnomAD database, including 52,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.29 (7078 hom., cov: 29)
  • Exomes 𝑓: 0.25 (45701 hom.)
• Consequence: LILRB4 NM_001278426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 21 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=5.827844E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB4	NM_001278426.4	c.13T>C	p.Phe5Leu	missense_variant	Exon 1 of 12	ENST00000695418.1	NP_001265355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1	c.13T>C	p.Phe5Leu	missense_variant	Exon 1 of 12		NM_001278426.4	ENSP00000511897.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44205 AN: 151718 Hom.: 7072 Cov.: 29

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.244 AC: 61099 AN: 250870 AF XY: 0.241

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.247 AC: 361680 AN: 1461454 Hom.: 45701 Cov.: 33 AF XY: 0.247 AC XY: 179260 AN XY: 727030

African (AFR) AF: 0.433 AC: 14494 AN: 33466

American (AMR) AF: 0.211 AC: 9438 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4869 AN: 26128

East Asian (EAS) AF: 0.215 AC: 8548 AN: 39686

South Asian (SAS) AF: 0.230 AC: 19819 AN: 86228

European-Finnish (FIN) AF: 0.217 AC: 11589 AN: 53398

Middle Eastern (MID) AF: 0.215 AC: 1237 AN: 5764

European-Non Finnish (NFE) AF: 0.249 AC: 276780 AN: 1111700

Other (OTH) AF: 0.247 AC: 14906 AN: 60378

GnomAD4 genome AF: 0.291 AC: 44252 AN: 151836 Hom.: 7078 Cov.: 29 AF XY: 0.287 AC XY: 21313 AN XY: 74212

African (AFR) AF: 0.429 AC: 17734 AN: 41382

American (AMR) AF: 0.234 AC: 3582 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1099 AN: 5136

South Asian (SAS) AF: 0.235 AC: 1124 AN: 4790

European-Finnish (FIN) AF: 0.215 AC: 2273 AN: 10556

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16917 AN: 67908

Other (OTH) AF: 0.267 AC: 561 AN: 2102

Alfa AF: 0.260 Hom.: 12294

Bravo AF: 0.296

TwinsUK AF: 0.241 AC: 894

ALSPAC AF: 0.259 AC: 997

ESP6500AA AF: 0.422 AC: 1861

ESP6500EA AF: 0.251 AC: 2156

ExAC AF: 0.253 AC: 30730

Asia WGS AF: 0.234 AC: 815 AN: 3478

EpiCase AF: 0.244

EpiControl AF: 0.242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.73
DANN	Benign	0.48
DEOGEN2	Benign	0.0028	.;.;T;.;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00088	N
LIST_S2	Benign	0.36	T;.;T;T;T;T
MetaRNN	Benign	0.00058	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.099
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.6	.;N;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	1.0	.;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	.;.;.;B;.;B
Vest4		0.061, 0.074, 0.093, 0.084
MutPred		0.43		.;Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);
MPC		0.014
ClinPred		0.0037	T
GERP RS		0.48
PromoterAI		0.016	Neutral
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs28366008; hg19: chr19-55174498; COSMIC: COSV54403480; COSMIC: COSV54403480;