rs731170

Variant names:

• chr19-54664811-G-A
• rs731170
• NM_001278426.4:c.668G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54664811-G-A
• chr19-54664811-G-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.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
• Publications: 32 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=0.0023657084).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

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.668G>A	p.Gly223Asp	missense	Exon 5 of 12	NP_001265355.2
	LILRB4	NM_001394933.1		c.668G>A	p.Gly223Asp	missense	Exon 5 of 12	NP_001381862.1
	LILRB4	NM_001278428.4		c.668G>A	p.Gly223Asp	missense	Exon 5 of 12	NP_001265357.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB4	ENST00000695418.1	MANE Select	c.668G>A	p.Gly223Asp	missense	Exon 5 of 12	ENSP00000511897.1
	LILRB4	ENST00000430952.6	TSL:1	c.668G>A	p.Gly223Asp	missense	Exon 5 of 12	ENSP00000408995.2
	LILRB4	ENST00000391733.7	TSL:5	c.668G>A	p.Gly223Asp	missense	Exon 5 of 12	ENSP00000375613.3

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

African (AFR) AF: 0.577 AC: 19106 AN: 33086

American (AMR) AF: 0.398 AC: 17227 AN: 43250

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6417 AN: 25118

East Asian (EAS) AF: 0.234 AC: 9268 AN: 39594

South Asian (SAS) AF: 0.290 AC: 24405 AN: 84154

European-Finnish (FIN) AF: 0.304 AC: 16094 AN: 52884

Middle Eastern (MID) AF: 0.242 AC: 1378 AN: 5688

European-Non Finnish (NFE) AF: 0.312 AC: 344136 AN: 1104206

Other (OTH) AF: 0.324 AC: 19348 AN: 59762

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

African (AFR) AF: 0.574 AC: 23812 AN: 41458

American (AMR) AF: 0.386 AC: 5890 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1327 AN: 5170

South Asian (SAS) AF: 0.298 AC: 1438 AN: 4822

European-Finnish (FIN) AF: 0.296 AC: 3130 AN: 10566

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21055 AN: 67954

Other (OTH) AF: 0.355 AC: 749 AN: 2108

Alfa AF: 0.334 Hom.: 22752

Bravo AF: 0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.29
DEOGEN2	Benign	0.0029	T
LIST_S2	Benign	0.071	T
MetaRNN	Benign	0.0024	T
PhyloP100		-2.6
Sift4G	Benign	0.41	T
Vest4		0.13
gMVP		0.14

Splicing

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

Other links and lift over

dbSNP: rs731170; hg19: chr19-55176262;