rs731170

Positions:

• chr19-54664811-G-A
• chr19-54664811-G-C

Variant summary

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

The NM_001278426.4(LILRB4):​c.668G>A​(p.Gly223Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,599,766 control chromosomes in the GnomAD database, including 86,664 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 0.39 (12445 hom., cov: 32)
  • Exomes 𝑓: 0.32 (74219 hom.)
• Consequence: LILRB4 NM_001278426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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=0.0023657084).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB4	NM_001278426.4	c.668G>A	p.Gly223Asp	missense_variant	5/12	ENST00000695418.1	NP_001265355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1	c.668G>A	p.Gly223Asp	missense_variant	5/12		NM_001278426.4	ENSP00000511897.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58653 AN: 151906 Hom.: 12422 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.316 AC: 457379 AN: 1447742 Hom.: 74219 Cov.: 33 AF XY: 0.313 AC XY: 225178 AN XY: 719300

Gnomad4 AFR exome AF: 0.577

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.386 AC: 58736 AN: 152024 Hom.: 12445 Cov.: 32 AF XY: 0.384 AC XY: 28499 AN XY: 74310

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.355

Alfa AF: 0.319 Hom.: 11593

Bravo AF: 0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.29
DEOGEN2	Benign	0.0029	.;T;.;T;T
LIST_S2	Benign	0.071	.;T;T;T;T
MetaRNN	Benign	0.0024	T;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T
Vest4		0.13
gMVP		0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs731170; hg19: chr19-55176262;