Variant 19-54595271-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000251372.8(LILRA1):c.530G>T(p.Trp177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000602 in 1,612,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

LILRA1
ENST00000251372.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.11

Variant links:

Genes affected

LILRA1 (HGNC:6602): (leukocyte immunoglobulin like receptor A1) This gene encodes an activating member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein is predominantly expressed in B cells, interacts with major histocompatibility complex class I ligands, and contributes to the regulation of immune responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

LILRA1 links:

LILRA1 (HGNC:):

LILRA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04063505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA1	NM_006863.4 linkuse as main transcript	c.530G>T	p.Trp177Leu	missense_variant	5/10	ENST00000251372.8	NP_006854.1	O75019-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA1	ENST00000251372.8 linkuse as main transcript	c.530G>T	p.Trp177Leu	missense_variant	5/10	1	NM_006863.4	ENSP00000251372.3		O75019-1

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150328

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000891

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251464

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000791

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000399

AC:

AN:

150328

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000891

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000559

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

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

Dec 11, 2023

The c.530G>T (p.W177L) alteration is located in exon 5 (coding exon 4) of the LILRA1 gene. This alteration results from a G to T substitution at nucleotide position 530, causing the tryptophan (W) at amino acid position 177 to be replaced by a leucine (L). 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

0.099

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0030

DANN

Benign

0.54

DEOGEN2

Benign

0.0025

T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0026

M_CAP

Benign

0.00096

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.51

N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.021

Sift

Benign

0.47

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.0010

B;B

Vest4

0.14

MutPred

0.47

Gain of methylation at R179 (P = 0.037);Gain of methylation at R179 (P = 0.037);

MVP

0.25

MPC

0.035

ClinPred

0.037

GERP RS

-4.2

Varity_R

0.035

gMVP

0.062

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