chr19-54274811-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080978.4(LILRB2):​c.1666C>T​(p.Pro556Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,613,210 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00059 ( 1 hom., cov: 30)
Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

LILRB2
NM_001080978.4 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227
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 Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009287894).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LILRB2NM_001080978.4 linkuse as main transcriptc.1666C>T p.Pro556Ser missense_variant 14/14 ENST00000314446.10 NP_001074447.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LILRB2ENST00000314446.10 linkuse as main transcriptc.1666C>T p.Pro556Ser missense_variant 14/141 NM_001080978.4 ENSP00000319960 A2Q8N423-2

Frequencies

GnomAD3 genomes
AF:
0.000588
AC:
89
AN:
151258
Hom.:
1
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000707
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00165
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000425
Gnomad FIN
AF:
0.000755
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.00194
GnomAD3 exomes
AF:
0.000589
AC:
148
AN:
251282
Hom.:
1
AF XY:
0.000663
AC XY:
90
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.000620
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.000326
Gnomad SAS exome
AF:
0.000915
Gnomad FIN exome
AF:
0.00125
Gnomad NFE exome
AF:
0.000510
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000414
AC:
605
AN:
1461834
Hom.:
1
Cov.:
31
AF XY:
0.000418
AC XY:
304
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000823
Gnomad4 FIN exome
AF:
0.00133
Gnomad4 NFE exome
AF:
0.000343
Gnomad4 OTH exome
AF:
0.000762
GnomAD4 genome
AF:
0.000588
AC:
89
AN:
151376
Hom.:
1
Cov.:
30
AF XY:
0.000676
AC XY:
50
AN XY:
73946
show subpopulations
Gnomad4 AFR
AF:
0.000705
Gnomad4 AMR
AF:
0.00164
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000425
Gnomad4 FIN
AF:
0.000755
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.00192
Alfa
AF:
0.000491
Hom.:
0
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000774
AC:
94
EpiCase
AF:
0.000491
EpiControl
AF:
0.000415

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 GeneticsDec 27, 2023The c.1669C>T (p.P557S) alteration is located in exon 14 (coding exon 13) of the LILRB2 gene. This alteration results from a C to T substitution at nucleotide position 1669, causing the proline (P) at amino acid position 557 to be replaced by a serine (S). 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
-0.57
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
12
DANN
Benign
0.43
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.0033
N
LIST_S2
Benign
0.72
.;.;T;.
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.0093
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-3.7
D;D;D;D
REVEL
Benign
0.040
Sift
Benign
0.17
T;T;T;T
Sift4G
Benign
0.096
T;T;T;T
Vest4
0.039
MVP
0.11
MPC
0.047
ClinPred
0.014
T
GERP RS
-2.6
gMVP
0.11

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: rs150493192; hg19: chr19-54778665; COSMIC: COSV58745429; API