Genetic Variant LILRB4:p.Asn335Asp (chr19-54666711-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

26 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LILRB4	NM_001278426.4 link	c.1003A>G	p.Asn335Asp	missense_variant	Exon 10 of 12	ENST00000695418.1	NP_001265355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1 link	c.1003A>G	p.Asn335Asp	missense_variant	Exon 10 of 12		NM_001278426.4	ENSP00000511897.1

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

GnomAD2 exomes

AF:

0.374

AC:

93981

AN:

251370

AF XY:

0.378

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 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

African (AFR)

AF:

0.414

AC:

13867

AN:

33472

American (AMR)

AF:

0.374

AC:

16703

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

6917

AN:

26132

East Asian (EAS)

AF:

0.552

AC:

21921

AN:

39696

South Asian (SAS)

AF:

0.542

AC:

46730

AN:

86248

European-Finnish (FIN)

AF:

0.400

AC:

21349

AN:

53412

Middle Eastern (MID)

AF:

0.342

AC:

1972

AN:

5766

European-Non Finnish (NFE)

AF:

0.288

AC:

320355

AN:

1111262

Other (OTH)

AF:

0.339

AC:

20468

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

16358

32716

49073

65431

81789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10926

21852

32778

43704

54630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.355

AC:

54048

AN:

152138

Hom.:

10047

Cov.:

AF XY:

0.365

AC XY:

27170

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.408

AC:

16966

AN:

41542

American (AMR)

AF:

0.360

AC:

5502

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

898

AN:

3470

East Asian (EAS)

AF:

0.557

AC:

2874

AN:

5164

South Asian (SAS)

AF:

0.559

AC:

2691

AN:

4818

European-Finnish (FIN)

AF:

0.405

AC:

4278

AN:

10572

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.290

AC:

19735

AN:

67964

Other (OTH)

AF:

0.329

AC:

696

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1786

3573

5359

7146

8932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0

.;T;.;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00013

LIST_S2

Benign

0.0

.;T;T;T;T

MetaRNN

Benign

0.000028

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;.;.;.

PhyloP100

0.012

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

Vest4

0.096

ClinPred

0.0014

GERP RS

-3.5

gMVP

0.016

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over