Variant 19-54337643-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012276.5(LILRA4):c.709G>A(p.Gly237Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

LILRA4
NM_012276.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.302

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:

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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=0.15854335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA4	NM_012276.5 linkuse as main transcript	c.709G>A	p.Gly237Arg	missense_variant	5/8	ENST00000291759.5	NP_036408.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA4	ENST00000291759.5 linkuse as main transcript	c.709G>A	p.Gly237Arg	missense_variant	5/8	2	NM_012276.5	ENSP00000291759	P1	P59901-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

249964

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.000315

Gnomad AMR exome

AF:

0.0000869

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:

0.0000266

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461306

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000145

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000494

AC:

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

Mar 01, 2023

The c.709G>A (p.G237R) alteration is located in exon 5 (coding exon 5) of the LILRA4 gene. This alteration results from a G to A substitution at nucleotide position 709, causing the glycine (G) at amino acid position 237 to be replaced by an arginine (R). 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

0.18

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.058

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.018

M_CAP

Benign

0.0036

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-7.3

REVEL

Benign

0.065

Sift

Uncertain

0.012

Sift4G

Pathogenic

0.0010

Vest4

0.41

MutPred

0.81

Gain of solvent accessibility (P = 0.0023);

MVP

0.19

MPC

0.41

ClinPred

0.57

GERP RS

2.5

gMVP

0.48

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.

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