Genetic Variant LILRA4:p.Ser400Asn (chr19-54336897-C-T) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

LILRA4 links:

ENSG00000275210 (HGNC:):

ENSG00000275210 links:

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
LILRA4	NM_012276.5 link	c.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	UniProt
LILRA4	ENST00000291759.5 link	c.1199G>A	p.Ser400Asn	missense_variant	Exon 6 of 8	2	NM_012276.5	ENSP00000291759.4	P59901-1
LILRA4	ENST00000595581.1 link	n.296G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3		ENSP00000471722.1	A0A075B7A5
ENSG00000275210	ENST00000616950.1 link	n.272G>A		non_coding_transcript_exon_variant	Exon 1 of 8	3

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152226

Hom.:

Cov.:

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:

AN:

251438

Hom.:

AF XY:

0.0000589

AC XY:

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:

AN:

1461636

Hom.:

Cov.:

137

AF XY:

0.0000371

AC XY:

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:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

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.:

ExAC

AF:

0.0000412

AC:

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

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

M_CAP

Benign

0.0036

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.9

REVEL

Benign

0.028

Sift

Benign

0.28

Sift4G

Benign

0.24

Vest4

0.21

MVP

0.11

MPC

0.16

ClinPred

0.031

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over