19-54636494-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001081637.3(LILRB1):​c.1654C>A​(p.Gln552Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000627 in 1,611,288 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000045 ( 1 hom. )

Consequence

LILRB1
NM_001081637.3 missense, splice_region

Scores

17
Splicing: ADA: 0.00004858
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.153
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04632622).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LILRB1NM_001081637.3 linkc.1654C>A p.Gln552Lys missense_variant, splice_region_variant Exon 14 of 15 ENST00000324602.12 NP_001075106.2 Q8NHL6A0A087WSV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LILRB1ENST00000324602.12 linkc.1654C>A p.Gln552Lys missense_variant, splice_region_variant Exon 14 of 15 5 NM_001081637.3 ENSP00000315997.7 A0A087WSV6

Frequencies

GnomAD3 genomes
AF:
0.000231
AC:
35
AN:
151820
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000751
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000388
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000727
AC:
18
AN:
247628
Hom.:
0
AF XY:
0.0000598
AC XY:
8
AN XY:
133728
show subpopulations
Gnomad AFR exome
AF:
0.000436
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000326
Gnomad SAS exome
AF:
0.0000663
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.0000452
AC:
66
AN:
1459468
Hom.:
1
Cov.:
39
AF XY:
0.0000344
AC XY:
25
AN XY:
726040
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.000731
GnomAD4 genome
AF:
0.000231
AC:
35
AN:
151820
Hom.:
0
Cov.:
31
AF XY:
0.000256
AC XY:
19
AN XY:
74146
show subpopulations
Gnomad4 AFR
AF:
0.000751
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.000227
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1654C>A (p.Q552K) alteration is located in exon 14 (coding exon 13) of the LILRB1 gene. This alteration results from a C to A substitution at nucleotide position 1654, causing the glutamine (Q) at amino acid position 552 to be replaced by a lysine (K). 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
-0.60
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
14
DANN
Benign
0.55
DEOGEN2
Benign
0.026
.;.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.47
T;T;T;.
M_CAP
Benign
0.00088
T
MetaRNN
Benign
0.046
T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.30
N;N;N;N
REVEL
Benign
0.0040
Sift
Benign
0.79
T;T;T;T
Sift4G
Benign
0.97
T;T;T;T
Vest4
0.14
MVP
0.055
MPC
0.070
ClinPred
0.0024
T
GERP RS
-2.7
gMVP
0.030

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000049
dbscSNV1_RF
Benign
0.0
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: rs373290406; hg19: chr19-55147945; API