19-54220564-A-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006864.4(LILRB3):c.1222T>A(p.Ser408Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00015 ( 2 hom., cov: 18)
Exomes 𝑓: 0.000017 ( 2 hom. )
Failed GnomAD Quality Control
Consequence
LILRB3
NM_006864.4 missense
NM_006864.4 missense
Scores
12
Clinical Significance
Conservation
PhyloP100: 1.07
Genes affected
LILRB3 (HGNC:6607): (leukocyte immunoglobulin like receptor B3) 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]
RPS9 (HGNC:10442): (ribosomal protein S9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14835685).
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LILRB3 | NM_006864.4 | c.1222T>A | p.Ser408Thr | missense_variant | 6/13 | ENST00000445347.2 | |
LOC124904768 | XR_007067339.1 | n.710+960A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LILRB3 | ENST00000445347.2 | c.1222T>A | p.Ser408Thr | missense_variant | 6/13 | 2 | NM_006864.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000146 AC: 16AN: 109960Hom.: 2 Cov.: 18
GnomAD3 genomes
?
AF:
AC:
16
AN:
109960
Hom.:
Cov.:
18
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000173 AC: 22AN: 1271992Hom.: 2 Cov.: 41 AF XY: 0.0000204 AC XY: 13AN XY: 635882
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
22
AN:
1271992
Hom.:
Cov.:
41
AF XY:
AC XY:
13
AN XY:
635882
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000145 AC: 16AN: 110032Hom.: 2 Cov.: 18 AF XY: 0.000131 AC XY: 7AN XY: 53300
GnomAD4 genome
?
AF:
AC:
16
AN:
110032
Hom.:
Cov.:
18
AF XY:
AC XY:
7
AN XY:
53300
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
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 submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.1222T>A (p.S408T) alteration is located in exon 6 (coding exon 6) of the LILRB3 gene. This alteration results from a T to A substitution at nucleotide position 1222, causing the serine (S) at amino acid position 408 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N
PROVEAN
Benign
N;N;N
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Vest4
MutPred
Gain of glycosylation at S408 (P = 0.0144);Gain of glycosylation at S408 (P = 0.0144);Gain of glycosylation at S408 (P = 0.0144);
MVP
ClinPred
T
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at