Genetic Variant LILRB3:p.Arg605Leu (chr19-54217175-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006864.4(LILRB3):c.1814G>T(p.Arg605Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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. R605Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

LILRB3
NM_006864.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.20

Publications

2 publications found

Variant links:

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]

LILRB3 links:

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]

RPS9 links:

ENSG00000300027 (HGNC:):

ENSG00000300027 links:

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ACMG classification

Classification was made for transcript

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=0.084775895).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRB3	NM_006864.4	MANE Select	c.1814G>T	p.Arg605Leu	missense	Exon 13 of 13	NP_006855.3	C9JWL8
LILRB3	NM_001320960.2		c.1865G>T	p.Arg622Leu	missense	Exon 14 of 14	NP_001307889.1
LILRB3	NM_001081450.3		c.1817G>T	p.Arg606Leu	missense	Exon 13 of 13	NP_001074919.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRB3	ENST00000445347.2	TSL:2 MANE Select	c.1814G>T	p.Arg605Leu	missense	Exon 13 of 13	ENSP00000388199.2	C9JWL8
LILRB3	ENST00000245620.13	TSL:1	c.1817G>T	p.Arg606Leu	missense	Exon 13 of 13	ENSP00000245620.9	O75022
LILRB3	ENST00000414379.5	TSL:1	n.*1321G>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000416920.1	F8WD89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.45

(source)

DANN

Benign

0.97

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0037

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0062

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.1

PhyloP100

-5.2

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.097

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.0080

Vest4

0.16

MVP

0.14

MPC

0.11

ClinPred

0.88

GERP RS

-5.8

gMVP

0.098

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over