19-54250920-C-G

Variant names:

• chr19-54250920-C-G
• rs1473576734
• NM_001081442.3:c.1642G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001081442.3(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. 13/20 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 NM_001081442.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

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]

ACMG classification

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=0.13764039).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081442.3. 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
	LILRB5	NM_001081442.3	MANE Select	c.1642G>C	p.Glu548Gln	missense	Exon 13 of 13	NP_001074911.2	O75023-3
	LILRB5	NM_001304457.3		c.1852G>C	p.Glu618Gln	missense	Exon 13 of 13	NP_001291386.2
	LILRB5	NM_006840.5		c.1639G>C	p.Glu547Gln	missense	Exon 13 of 13	NP_006831.2	O75023-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB5	ENST00000449561.3	TSL:1 MANE Select	c.1642G>C	p.Glu548Gln	missense	Exon 13 of 13	ENSP00000406478.1	O75023-3
	LILRB5	ENST00000316219.9	TSL:1	c.1639G>C	p.Glu547Gln	missense	Exon 13 of 13	ENSP00000320390.5	O75023-1
	LILRB5	ENST00000867152.1		c.1825G>C	p.Glu609Gln	missense	Exon 12 of 12	ENSP00000537211.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-0.80	T
PhyloP100		1.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.040
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.21	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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1473576734; hg19: chr19-54754784;