19-54636735-G-A

Variant summary

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

The NM_001081637.3(LILRB1):​c.1816G>A​(p.Ala606Thr) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LILRB1
NM_001081637.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110
Variant links:
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]
LILRB1-AS1 (HGNC:53114): (LILRB1 antisense RNA 1)

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=0.12405509).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LILRB1NM_001081637.3 linkc.1816G>A p.Ala606Thr missense_variant Exon 15 of 15 ENST00000324602.12 NP_001075106.2 Q8NHL6A0A087WSV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LILRB1ENST00000324602.12 linkc.1816G>A p.Ala606Thr missense_variant Exon 15 of 15 5 NM_001081637.3 ENSP00000315997.7 A0A087WSV6

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.85e-7
AC:
1
AN:
1459526
Hom.:
0
Cov.:
45
AF XY:
0.00000138
AC XY:
1
AN XY:
725794
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
27

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 09, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1816G>A (p.A606T) alteration is located in exon 15 (coding exon 14) of the LILRB1 gene. This alteration results from a G to A substitution at nucleotide position 1816, causing the alanine (A) at amino acid position 606 to be replaced by a threonine (T). 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
-0.60
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.036
T;T;.;.;T;.;.
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.0064
N
LIST_S2
Benign
0.74
T;T;T;T;T;T;.
M_CAP
Benign
0.00083
T
MetaRNN
Benign
0.12
T;T;T;T;T;T;T
MetaSVM
Benign
-0.88
T
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.8
N;N;N;N;N;N;N
REVEL
Benign
0.025
Sift
Benign
0.058
T;T;T;T;T;T;T
Sift4G
Benign
0.14
T;T;T;T;T;T;T
Polyphen
0.78
.;.;.;.;.;P;.
Vest4
0.10
MutPred
0.23
Loss of loop (P = 0.0128);.;.;.;.;.;.;
MVP
0.19
MPC
0.21
ClinPred
0.35
T
GERP RS
-0.66
gMVP
0.042

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr19-55148186; API