chr19-54219161-A-C

Variant names:

• chr19-54219161-A-C
• rs61734493
• NM_006864.4:c.1394T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006864.4(LILRB3):​c.1394T>G​(p.Leu465Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 1,606,838 control chromosomes in the GnomAD database, including 693,766 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L465H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.95 (67802 hom., cov: 27)
  • Exomes 𝑓: 0.93 (625964 hom.)
• Consequence: LILRB3 NM_006864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 10 publications found

Genes affected

LILRB3 (HGNC:6607): (leukocyte immunoglobulin like receptor B3) 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. 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]

LOC124904768 (HGNC:):

RPS9 (HGNC:10442): (ribosomal protein S9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004377067).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB3	NM_006864.4	MANE Select	c.1394T>G	p.Leu465Arg	missense	Exon 8 of 13	NP_006855.3	C9JWL8
	LILRB3	NM_001320960.2		c.1445T>G	p.Leu482Arg	missense	Exon 9 of 14	NP_001307889.1
	LILRB3	NM_001081450.3		c.1394T>G	p.Leu465Arg	missense	Exon 8 of 13	NP_001074919.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB3	ENST00000445347.2	TSL:2 MANE Select	c.1394T>G	p.Leu465Arg	missense	Exon 8 of 13	ENSP00000388199.2	C9JWL8
	LILRB3	ENST00000245620.13	TSL:1	c.1394T>G	p.Leu465Arg	missense	Exon 8 of 13	ENSP00000245620.9	O75022
	LILRB3	ENST00000414379.5	TSL:1	n.*901T>G		non_coding_transcript_exon	Exon 9 of 14	ENSP00000416920.1	F8WD89

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143061 AN: 151372 Hom.: 67745 Cov.: 27

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.961

GnomAD4 exome AF: 0.927 AC: 1349049 AN: 1455348 Hom.: 625964 Cov.: 59 AF XY: 0.929 AC XY: 672893 AN XY: 724380

African (AFR) AF: 0.988 AC: 32612 AN: 33002

American (AMR) AF: 0.980 AC: 42218 AN: 43096

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 25197 AN: 25762

East Asian (EAS) AF: 1.00 AC: 39666 AN: 39674

South Asian (SAS) AF: 0.995 AC: 85555 AN: 85956

European-Finnish (FIN) AF: 0.878 AC: 46679 AN: 53162

Middle Eastern (MID) AF: 0.997 AC: 5701 AN: 5720

European-Non Finnish (NFE) AF: 0.915 AC: 1014693 AN: 1108924

Other (OTH) AF: 0.945 AC: 56728 AN: 60052

GnomAD4 genome AF: 0.945 AC: 143177 AN: 151490 Hom.: 67802 Cov.: 27 AF XY: 0.946 AC XY: 69913 AN XY: 73922

African (AFR) AF: 0.985 AC: 40736 AN: 41348

American (AMR) AF: 0.976 AC: 14871 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3393 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5071 AN: 5072

South Asian (SAS) AF: 0.997 AC: 4755 AN: 4770

European-Finnish (FIN) AF: 0.868 AC: 9076 AN: 10462

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62181 AN: 67822

Other (OTH) AF: 0.960 AC: 2022 AN: 2106

Alfa AF: 0.949 Hom.: 31931

Bravo AF: 0.954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.030
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
LIST_S2	Benign	0.060	T
MetaRNN	Benign	0.0044	T
PhyloP100		-0.093
Sift4G	Benign	0.42	T
Vest4		0.29
gMVP		0.13

Splicing

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

Other links and lift over

dbSNP: rs61734493; hg19: chr19-54723030;