19-54631962-C-T

Variant summary

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

The NM_001081637.3(LILRB1):c.386C>T(p.Ala129Val) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 44)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.382

Genes affected

LILRB1 (HGNC:6605): (leukocyte immunoglobulin like receptor B1) 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). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. 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=0.19684112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LILRB1	NM_001081637.3	c.386C>T	p.Ala129Val	missense_variant	5/15	ENST00000324602.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LILRB1	ENST00000324602.12	c.386C>T	p.Ala129Val	missense_variant	5/15	5	NM_001081637.3	P4

Frequencies

GnomAD3 genomes Cov.: 44

GnomAD4 exome Cov.: 99

GnomAD4 genome Cov.: 44

Bravo AF: 0.00000378

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

Mar 06, 2023

The c.386C>T (p.A129V) alteration is located in exon 5 (coding exon 4) of the LILRB1 gene. This alteration results from a C to T substitution at nucleotide position 386, causing the alanine (A) at amino acid position 129 to be replaced by a valine (V). 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
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	14
Dann	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.;.;T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.84	T;T;T;T;T;T;.
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.9	D;D;D;D;D;D;D
REVEL	Benign	0.028
Sift	Benign	0.10	T;T;T;T;T;T;T
Sift4G	Benign	0.086	T;T;T;T;T;T;T
Polyphen		1.0	.;.;.;.;.;D;.
Vest4		0.18
MutPred		0.69		Gain of catalytic residue at S132 (P = 0.0902);Gain of catalytic residue at S132 (P = 0.0902);Gain of catalytic residue at S132 (P = 0.0902);Gain of catalytic residue at S132 (P = 0.0902);.;Gain of catalytic residue at S132 (P = 0.0902);Gain of catalytic residue at S132 (P = 0.0902);
MVP		0.29
MPC		0.27
ClinPred		0.56	D
GERP RS		0.50
gMVP		0.046

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

LitVar

Other links and lift over

dbSNP: rs1187615791; hg19: chr19-55143413;