19-54632085-C-T

Variant summary

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

The NM_001081637.3(LILRB1):​c.509C>T​(p.Ser170Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,880 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 0.000013 ( 0 hom., cov: 42)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LILRB1
NM_001081637.3 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0990
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]

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=0.14047804).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LILRB1NM_001081637.3 linkc.509C>T p.Ser170Phe missense_variant Exon 5 of 15 ENST00000324602.12 NP_001075106.2 Q8NHL6A0A087WSV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LILRB1ENST00000324602.12 linkc.509C>T p.Ser170Phe missense_variant Exon 5 of 15 5 NM_001081637.3 ENSP00000315997.7 A0A087WSV6

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
152262
Hom.:
0
Cov.:
42
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251482
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461880
Hom.:
0
Cov.:
159
AF XY:
0.00000963
AC XY:
7
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
0.00000629
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000131
AC:
2
AN:
152262
Hom.:
0
Cov.:
42
AF XY:
0.0000134
AC XY:
1
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000301
Hom.:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
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
Feb 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.509C>T (p.S170F) alteration is located in exon 5 (coding exon 4) of the LILRB1 gene. This alteration results from a C to T substitution at nucleotide position 509, causing the serine (S) at amino acid position 170 to be replaced by a phenylalanine (F). 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
-0.37
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.093
T;T;.;.;T;.;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.75
T;T;T;T;T;T;.
M_CAP
Benign
0.00066
T
MetaRNN
Benign
0.14
T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
PrimateAI
Benign
0.30
T
PROVEAN
Pathogenic
-5.1
D;D;D;D;D;D;D
REVEL
Benign
0.053
Sift
Uncertain
0.0020
D;D;D;D;D;D;D
Sift4G
Uncertain
0.038
D;D;D;T;D;D;T
Polyphen
1.0
.;.;.;.;.;D;.
Vest4
0.18
MutPred
0.35
Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);.;Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);
MVP
0.19
MPC
0.37
ClinPred
0.75
D
GERP RS
-3.1
gMVP
0.050

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs750167334; hg19: chr19-55143536; API