rs1048801

Positions:

• chr19-54667913-G-A
• chr19-54667913-G-C
• chr19-54667913-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278426.4(LILRB4):​c.1241G>A​(p.Arg414Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,606,050 control chromosomes in the GnomAD database, including 326,476 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 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 0.62 (28098 hom., cov: 24)
  • Exomes 𝑓: 0.64 (298378 hom.)
• Consequence: LILRB4 NM_001278426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0076108873).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB4	NM_001278426.4	c.1241G>A	p.Arg414Gln	missense_variant	12/12	ENST00000695418.1	NP_001265355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1	c.1241G>A	p.Arg414Gln	missense_variant	12/12		NM_001278426.4	ENSP00000511897	A2

Frequencies

GnomAD3 genomes AF: 0.618 AC: 91484 AN: 148104 Hom.: 28077 Cov.: 24

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.639 AC: 932037 AN: 1457840 Hom.: 298378 Cov.: 75 AF XY: 0.637 AC XY: 462336 AN XY: 725290

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.699

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.666

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.632

GnomAD4 genome AF: 0.618 AC: 91542 AN: 148210 Hom.: 28098 Cov.: 24 AF XY: 0.620 AC XY: 44730 AN XY: 72108

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.615

Alfa AF: 0.616 Hom.: 12913

Bravo AF: 0.605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DEOGEN2	Benign	0.0021	.;T;.;T
LIST_S2	Benign	0.64	.;T;T;T
MetaRNN	Benign	0.0076	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.092
gMVP		0.025

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1048801; hg19: chr19-55179364;