chr19-54274723-G-A

Variant summary

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

The NM_001080978.4(LILRB2):​c.1754C>T​(p.Pro585Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

LILRB2
NM_001080978.4 missense

Scores

1
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.413
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=0.10012829).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LILRB2NM_001080978.4 linkuse as main transcriptc.1754C>T p.Pro585Leu missense_variant 14/14 ENST00000314446.10 NP_001074447.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LILRB2ENST00000314446.10 linkuse as main transcriptc.1754C>T p.Pro585Leu missense_variant 14/141 NM_001080978.4 ENSP00000319960 A2Q8N423-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152046
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:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000175
AC:
44
AN:
251286
Hom.:
1
AF XY:
0.000140
AC XY:
19
AN XY:
135806
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000334
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.0000636
AC:
93
AN:
1461740
Hom.:
0
Cov.:
30
AF XY:
0.0000426
AC XY:
31
AN XY:
727152
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:
0.000206
Gnomad4 NFE exome
AF:
0.0000620
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152046
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74244
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:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000279
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.000330
AC:
40

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 GeneticsOct 12, 2022The c.1757C>T (p.P586L) alteration is located in exon 14 (coding exon 13) of the LILRB2 gene. This alteration results from a C to T substitution at nucleotide position 1757, causing the proline (P) at amino acid position 586 to be replaced by a leucine (L). 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
-0.36
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
14
DANN
Uncertain
0.99
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.018
N
LIST_S2
Uncertain
0.96
.;.;D;.
M_CAP
Benign
0.00075
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-0.91
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Pathogenic
-5.0
D;D;D;D
REVEL
Benign
0.024
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.020
D;D;D;D
Vest4
0.087
MVP
0.30
MPC
0.31
ClinPred
0.35
T
GERP RS
1.3
gMVP
0.097

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

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

Other links and lift over

dbSNP: rs202182093; hg19: chr19-54778577; API