19-54667913-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001278426.4(LILRB4):​c.1241G>T​(p.Arg414Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/8 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: not found (cov: 24)
  • Exomes 𝑓: 6.9e-7 (0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13027433).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB4	NM_001278426.4	MANE Select	c.1241G>T	p.Arg414Leu	missense	Exon 12 of 12	NP_001265355.2
	LILRB4	NM_001394933.1		c.1244G>T	p.Arg415Leu	missense	Exon 12 of 12	NP_001381862.1
	LILRB4	NM_001278428.4		c.1241G>T	p.Arg414Leu	missense	Exon 12 of 12	NP_001265357.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB4	ENST00000695418.1	MANE Select	c.1241G>T	p.Arg414Leu	missense	Exon 12 of 12	ENSP00000511897.1
	LILRB4	ENST00000430952.6	TSL:1	c.1238G>T	p.Arg413Leu	missense	Exon 12 of 12	ENSP00000408995.2
	LILRB4	ENST00000391733.7	TSL:5	c.1244G>T	p.Arg415Leu	missense	Exon 12 of 12	ENSP00000375613.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457978 Hom.: 0 Cov.: 75 AF XY: 0.00000138 AC XY: 1 AN XY: 725350

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109436

Other (OTH) AF: 0.00 AC: 0 AN: 60108

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DEOGEN2	Benign	0.025	T
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.13	T
PhyloP100		0.15
Sift4G	Pathogenic	0.0010	D
Vest4		0.17
gMVP		0.11

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: rs1048801; hg19: chr19-55179364;