19-54250920-C-T

Variant names:

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

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>A​(p.Glu548Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. E548Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LILRB5 NM_001081442.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 1 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=0.16220948).

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>A	p.Glu548Lys	missense	Exon 13 of 13	NP_001074911.2	O75023-3
	LILRB5	NM_001304457.3		c.1852G>A	p.Glu618Lys	missense	Exon 13 of 13	NP_001291386.2
	LILRB5	NM_006840.5		c.1639G>A	p.Glu547Lys	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>A	p.Glu548Lys	missense	Exon 13 of 13	ENSP00000406478.1	O75023-3
	LILRB5	ENST00000316219.9	TSL:1	c.1639G>A	p.Glu547Lys	missense	Exon 13 of 13	ENSP00000320390.5	O75023-1
	LILRB5	ENST00000867152.1		c.1825G>A	p.Glu609Lys	missense	Exon 12 of 12	ENSP00000537211.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250352 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460242 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726154

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110838

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.031	N
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.90	T
PhyloP100		1.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.051
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.012	D
Vest4		0.092
MutPred		0.39		Gain of ubiquitination at E547 (P = 0.0077)
MVP		0.42
MPC		0.26
ClinPred		0.85	D
GERP RS		0.21
gMVP		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;