19-54252085-T-C

Position:

• chr19-54252085-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000449561.3(LILRB5):​c.1598A>G​(p.Gln533Arg) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LILRB5 ENST00000449561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.443

Genes affected

LILRB5 (HGNC:6609): (leukocyte immunoglobulin like receptor B5) 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). Several other LIR subfamily B receptors are expressed on immune cells where they bind to MHC class I molecules on antigen-presenting cells and inhibit stimulation of an immune response. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

LILRB5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13756114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB5	NM_001081442.3	c.1598A>G	p.Gln533Arg	missense_variant	12/13	ENST00000449561.3	NP_001074911.2
LILRB5	NM_001304457.3	c.1571A>G	p.Gln524Arg	missense_variant	12/13		NP_001291386.2
LILRB5	NM_006840.5	c.1595A>G	p.Gln532Arg	missense_variant	12/13		NP_006831.2
LILRB5	NM_001081443.3	c.1298A>G	p.Gln433Arg	missense_variant	11/12		NP_001074912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB5	ENST00000449561.3	c.1598A>G	p.Gln533Arg	missense_variant	12/13	1	NM_001081442.3	ENSP00000406478.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.1598A>G (p.Q533R) alteration is located in exon 12 (coding exon 12) of the LILRB5 gene. This alteration results from a A to G substitution at nucleotide position 1598, causing the glutamine (Q) at amino acid position 533 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Uncertain	0.98
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.0072	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.055	T;T;T
Sift4G	Benign	0.088	T;T;T
Vest4		0.17
MVP		0.38
MPC		0.073
ClinPred		0.099	T
GERP RS		0.75
gMVP		0.059

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54755948;