19-54254791-C-T

Variant names:

• chr19-54254791-C-T
• NM_001081442.3:c.1199G>A

Variant summary

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

The NM_001081442.3(LILRB5):​c.1199G>A​(p.Arg400Lys) 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. 13/19 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. R400T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LILRB5 NM_001081442.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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

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=0.08848345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB5	NM_001081442.3	c.1199G>A	p.Arg400Lys	missense_variant	Exon 6 of 13	ENST00000449561.3	NP_001074911.2
LILRB5	NM_001304457.3	c.1172G>A	p.Arg391Lys	missense_variant	Exon 6 of 13		NP_001291386.2
LILRB5	NM_006840.5	c.1199G>A	p.Arg400Lys	missense_variant	Exon 6 of 13		NP_006831.2
LILRB5	NM_001081443.3	c.899G>A	p.Arg300Lys	missense_variant	Exon 5 of 12		NP_001074912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB5	ENST00000449561.3	c.1199G>A	p.Arg400Lys	missense_variant	Exon 6 of 13	1	NM_001081442.3	ENSP00000406478.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.1
DANN	Uncertain	0.98
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0073	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.21	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.041	D;D;D
Sift4G	Uncertain	0.040	D;T;D
Vest4		0.072
MVP		0.22
MPC		0.055
ClinPred		0.47	T
GERP RS		-1.4
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr19-54758654;