chr19-54276285-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.1573G>T​(p.Asp525Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000623 in 1,461,846 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: not found (cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

LILRB2
NM_001080978.4 missense

Scores

5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.929
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=0.15943936).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LILRB2NM_001080978.4 linkuse as main transcriptc.1573G>T p.Asp525Tyr missense_variant 12/14 ENST00000314446.10 NP_001074447.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LILRB2ENST00000314446.10 linkuse as main transcriptc.1573G>T p.Asp525Tyr missense_variant 12/141 NM_001080978.4 ENSP00000319960 A2Q8N423-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251242
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135852
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:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000623
AC:
91
AN:
1461846
Hom.:
0
Cov.:
32
AF XY:
0.0000605
AC XY:
44
AN XY:
727224
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:
0.0000800
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 GeneticsMar 23, 2023The c.1576G>T (p.D526Y) alteration is located in exon 12 (coding exon 11) of the LILRB2 gene. This alteration results from a G to T substitution at nucleotide position 1576, causing the aspartic acid (D) at amino acid position 526 to be replaced by a tyrosine (Y). 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
-0.16
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
17
DANN
Benign
0.95
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.0081
N
LIST_S2
Uncertain
0.90
.;.;D;.
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-4.0
D;D;D;D
REVEL
Benign
0.067
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D
Vest4
0.17
MVP
0.22
MPC
0.30
ClinPred
0.85
D
GERP RS
-0.46
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

LitVar

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

Other links and lift over

dbSNP: rs369899348; hg19: chr19-54780139; API