Variant 19-54666711-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001278426.4(LILRB4):c.1003A>G(p.Asn335Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,613,206 control chromosomes in the GnomAD database, including 90,327 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 10047 hom., cov: 33)

Exomes 𝑓: 0.32 ( 80280 hom. )

Consequence

LILRB4
NM_001278426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

Variant links:

Genes affected

LILRB4 (HGNC:6608): (leukocyte immunoglobulin like receptor B4) This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. The receptor can also function in antigen capture and presentation. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

LILRB4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8374105E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LILRB4	NM_001278426.4 linkuse as main transcript	c.1003A>G	p.Asn335Asp	missense_variant	10/12	ENST00000695418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LILRB4	ENST00000695418.1 linkuse as main transcript	c.1003A>G	p.Asn335Asp	missense_variant	10/12		NM_001278426.4	A2

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

54010

AN:

152020

Hom.:

10043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.374

AC:

93981

AN:

251370

Hom.:

19086

AF XY:

0.378

AC XY:

51372

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.417

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.571

Gnomad SAS exome

AF:

0.544

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.322

AC:

470282

AN:

1461068

Hom.:

80280

Cov.:

AF XY:

0.328

AC XY:

238426

AN XY:

726876

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.374

Gnomad4 ASJ exome

AF:

0.265

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.542

Gnomad4 FIN exome

AF:

0.400

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.355

AC:

54048

AN:

152138

Hom.:

10047

Cov.:

AF XY:

0.365

AC XY:

27170

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.290

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.237

Hom.:

990

Bravo

AF:

0.350

TwinsUK

AF:

0.270

AC:

1000

ALSPAC

AF:

0.273

AC:

1053

ESP6500AA

AF:

0.397

AC:

1749

ESP6500EA

AF:

0.285

AC:

2451

ExAC

AF:

0.376

AC:

45662

EpiCase

AF:

0.289

EpiControl

AF:

0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.0

DANN

Benign

0.67

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00013

MetaRNN

Benign

0.000028

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

1.4

N;N;N;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;.;B;.;B

Vest4

0.096

MPC

0.014

ClinPred

0.0014

GERP RS

-3.5

gMVP

0.016

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over