chr19-54276445-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080978.4(LILRB2):​c.1492G>T​(p.Ala498Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,593,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

LILRB2
NM_001080978.4 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.487
Variant links:
Genes affected
LILRB2 (HGNC:6606): (leukocyte immunoglobulin like receptor B2) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1198636).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LILRB2NM_001080978.4 linkuse as main transcriptc.1492G>T p.Ala498Ser missense_variant 11/14 ENST00000314446.10 NP_001074447.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LILRB2ENST00000314446.10 linkuse as main transcriptc.1492G>T p.Ala498Ser missense_variant 11/141 NM_001080978.4 ENSP00000319960 A2Q8N423-2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151978
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000347
AC:
5
AN:
1440964
Hom.:
0
Cov.:
31
AF XY:
0.00000421
AC XY:
3
AN XY:
713430
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000365
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 17, 2023The c.1495G>T (p.A499S) alteration is located in exon 11 (coding exon 10) of the LILRB2 gene. This alteration results from a G to T substitution at nucleotide position 1495, causing the alanine (A) at amino acid position 499 to be replaced by a serine (S). 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
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
7.2
DANN
Benign
0.91
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.0043
N
LIST_S2
Uncertain
0.92
.;.;D;.
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.72
N;N;N;N
REVEL
Benign
0.018
Sift
Benign
0.24
T;T;T;T
Sift4G
Benign
0.15
T;T;T;T
Vest4
0.12
MutPred
0.33
.;.;.;Gain of relative solvent accessibility (P = 0.0479);
MVP
0.27
MPC
0.16
ClinPred
0.21
T
GERP RS
-0.17
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2080232264; hg19: chr19-54780299; API