Variant 19-54336877-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012276.5(LILRA4):c.1219T>A(p.Ser407Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.0035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.021 ( 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: 1.31

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009393901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA4	NM_012276.5 linkuse as main transcript	c.1219T>A	p.Ser407Thr	missense_variant	6/8	ENST00000291759.5	NP_036408.4	P59901-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LILRA4	ENST00000291759.5 linkuse as main transcript	c.1219T>A	p.Ser407Thr	missense_variant	6/8	2	NM_012276.5	ENSP00000291759.4	P59901-1
LILRA4	ENST00000595581.1 linkuse as main transcript	n.316T>A		non_coding_transcript_exon_variant	2/2	3		ENSP00000471722.1	A0A075B7A5
ENSG00000275210	ENST00000616950.1 linkuse as main transcript	n.292T>A		non_coding_transcript_exon_variant	1/8	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

418

AN:

119036

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00496

Gnomad AMI

AF:

0.00434

Gnomad AMR

AF:

0.00384

Gnomad ASJ

AF:

0.00154

Gnomad EAS

AF:

0.00268

Gnomad SAS

AF:

0.00784

Gnomad FIN

AF:

0.00487

Gnomad MID

AF:

0.00410

Gnomad NFE

AF:

0.00220

Gnomad OTH

AF:

0.00635

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251416

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0206

AC:

19473

AN:

945454

Hom.:

Cov.:

136

AF XY:

0.0268

AC XY:

12416

AN XY:

462446

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.0429

Gnomad4 ASJ exome

AF:

0.0689

Gnomad4 EAS exome

AF:

0.00794

Gnomad4 SAS exome

AF:

0.0892

Gnomad4 FIN exome

AF:

0.0388

Gnomad4 NFE exome

AF:

0.0150

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00351

AC:

418

AN:

119176

Hom.:

Cov.:

AF XY:

0.00413

AC XY:

239

AN XY:

57850

show subpopulations

Gnomad4 AFR

AF:

0.00494

Gnomad4 AMR

AF:

0.00383

Gnomad4 ASJ

AF:

0.00154

Gnomad4 EAS

AF:

0.00268

Gnomad4 SAS

AF:

0.00780

Gnomad4 FIN

AF:

0.00487

Gnomad4 NFE

AF:

0.00220

Gnomad4 OTH

AF:

0.00626

Alfa

AF:

0.126

Hom.:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Sep 24, 2024

The c.1219T>A (p.S407T) alteration is located in exon 6 (coding exon 6) of the LILRA4 gene. This alteration results from a T to A substitution at nucleotide position 1219, causing the serine (S) at amino acid position 407 to be replaced by a threonine (T). 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

0.089

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.16

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0094

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.0

REVEL

Benign

0.039

Sift

Benign

0.079

Sift4G

Benign

0.074

Vest4

0.23

MVP

0.22

MPC

0.11

ClinPred

0.053

GERP RS

2.4

gMVP

0.48

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