NM_001278426.4:c.1241G>A

Variant names:

• chr19-54667913-G-A
• rs1048801
• NM_001278426.4:c.1241G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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=0.0076108873).
• 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 rank	MANE	Protein	UniProt
LILRB4	NM_001278426.4	c.1241G>A	p.Arg414Gln	missense_variant	Exon 12 of 12	ENST00000695418.1	NP_001265355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1	c.1241G>A	p.Arg414Gln	missense_variant	Exon 12 of 12		NM_001278426.4	ENSP00000511897.1

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

African (AFR) AF: 0.539 AC: 17908 AN: 33226

American (AMR) AF: 0.619 AC: 27606 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 15743 AN: 25942

East Asian (EAS) AF: 0.699 AC: 27626 AN: 39550

South Asian (SAS) AF: 0.593 AC: 51113 AN: 86214

European-Finnish (FIN) AF: 0.666 AC: 35422 AN: 53156

Middle Eastern (MID) AF: 0.609 AC: 3500 AN: 5750

European-Non Finnish (NFE) AF: 0.645 AC: 715164 AN: 1109338

Other (OTH) AF: 0.632 AC: 37955 AN: 60102

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

African (AFR) AF: 0.544 AC: 21626 AN: 39724

American (AMR) AF: 0.656 AC: 9698 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2086 AN: 3444

East Asian (EAS) AF: 0.707 AC: 3481 AN: 4924

South Asian (SAS) AF: 0.624 AC: 2876 AN: 4606

European-Finnish (FIN) AF: 0.679 AC: 6895 AN: 10148

Middle Eastern (MID) AF: 0.657 AC: 188 AN: 286

European-Non Finnish (NFE) AF: 0.635 AC: 42728 AN: 67324

Other (OTH) AF: 0.615 AC: 1262 AN: 2052

Alfa AF: 0.619 Hom.: 17865

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
PhyloP100		0.15
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

Other links and lift over

dbSNP: rs1048801; hg19: chr19-55179364;