19-54336897-C-T

Variant summary

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

The NM_012276.5(LILRA4):​c.1199G>A​(p.Ser400Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000037 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LILRA4
NM_012276.5 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
LILRA4 (HGNC:15503): (leukocyte immunoglobulin like receptor A4) This gene encodes an immunoglobulin-like cell surface protein that is expressed predominantly on plasmacytoid dendritic cells (PDCs) and modulates the function of these cells in the immune response. Expression of this gene is downregulated by interleukin 3 (IL3). This gene is one of a cluster of highly related genes located at chromosomal region 19q13.4. [provided by RefSeq, Jan 2015]

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=0.10535839).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LILRA4NM_012276.5 linkc.1199G>A p.Ser400Asn missense_variant Exon 6 of 8 ENST00000291759.5 NP_036408.4 P59901-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LILRA4ENST00000291759.5 linkc.1199G>A p.Ser400Asn missense_variant Exon 6 of 8 2 NM_012276.5 ENSP00000291759.4 P59901-1
LILRA4ENST00000595581.1 linkn.296G>A non_coding_transcript_exon_variant Exon 2 of 2 3 ENSP00000471722.1 A0A075B7A5
ENSG00000275210ENST00000616950.1 linkn.272G>A non_coding_transcript_exon_variant Exon 1 of 8 3

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152226
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000217
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:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000437
AC:
11
AN:
251438
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000369
AC:
54
AN:
1461636
Hom.:
0
Cov.:
137
AF XY:
0.0000371
AC XY:
27
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152226
Hom.:
0
Cov.:
34
AF XY:
0.000134
AC XY:
10
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.000217
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:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000190
Hom.:
0
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1199G>A (p.S400N) alteration is located in exon 6 (coding exon 6) of the LILRA4 gene. This alteration results from a G to A substitution at nucleotide position 1199, causing the serine (S) at amino acid position 400 to be replaced by an asparagine (N). 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
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
5.7
DANN
Benign
0.92
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0095
N
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.92
T
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.028
Sift
Benign
0.28
T
Sift4G
Benign
0.24
T
Vest4
0.21
MVP
0.11
MPC
0.16
ClinPred
0.031
T
GERP RS
-4.0
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: rs762916224; hg19: chr19-54848168; API