chr19-54250920-C-G

Position:

• chr19-54250920-C-G

Variant summary

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

The ENST00000449561.3(LILRB5):​c.1642G>C​(p.Glu548Gln) 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: 25)
• Consequence: LILRB5 ENST00000449561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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=0.13764039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB5	NM_001081442.3	c.1642G>C	p.Glu548Gln	missense_variant	13/13	ENST00000449561.3	NP_001074911.2
LILRB5	NM_001304457.3	c.1852G>C	p.Glu618Gln	missense_variant	13/13		NP_001291386.2
LILRB5	NM_006840.5	c.1639G>C	p.Glu547Gln	missense_variant	13/13		NP_006831.2
LILRB5	NM_001081443.3	c.1342G>C	p.Glu448Gln	missense_variant	12/12		NP_001074912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB5	ENST00000449561.3	c.1642G>C	p.Glu548Gln	missense_variant	13/13	1	NM_001081442.3	ENSP00000406478.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 25

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

Feb 05, 2024

The c.1642G>C (p.E548Q) alteration is located in exon 13 (coding exon 13) of the LILRB5 gene. This alteration results from a G to C substitution at nucleotide position 1642, causing the glutamic acid (E) at amino acid position 548 to be replaced by a glutamine (Q). 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	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.040
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.21	T;T;T
Vest4		0.048
MutPred		0.24		Gain of loop (P = 0.1069);.;.;
MVP		0.45
MPC		0.28
ClinPred		0.51	D
GERP RS		0.21
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54754784;