Variant 19-54667725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001278426.4(LILRB4):c.1132C>T(p.Pro378Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,610,630 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 29)

Exomes 𝑓: 0.0043 ( 20 hom. )

Consequence

LILRB4
NM_001278426.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051362813).

BP6

Variant 19-54667725-C-T is Benign according to our data. Variant chr19-54667725-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650457.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB4	NM_001278426.4 link	c.1132C>T	p.Pro378Ser	missense_variant	11/12	ENST00000695418.1	NP_001265355.2	Q8NHJ6A0A8Q3SHR1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1 link	c.1132C>T	p.Pro378Ser	missense_variant	11/12		NM_001278426.4	ENSP00000511897.1		A0A8Q3SHR1

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

597

AN:

151504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00458

Gnomad FIN

AF:

0.0152

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.00289

GnomAD3 exomes

AF:

0.00571

AC:

1433

AN:

250876

Hom.:

AF XY:

0.00570

AC XY:

773

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00549

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.00524

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00426

AC:

6221

AN:

1459008

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

3194

AN XY:

725724

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00611

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.00350

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.00394

AC:

597

AN:

151622

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

321

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.00141

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00459

Gnomad4 FIN

AF:

0.0152

Gnomad4 NFE

AF:

0.00367

Gnomad4 OTH

AF:

0.00286

Alfa

AF:

0.00516

Hom.:

Bravo

AF:

0.00286

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00559

AC:

679

EpiCase

AF:

0.00425

EpiControl

AF:

0.00504

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

LILRB4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.11

DANN

Benign

0.53

DEOGEN2

Benign

0.019

.;T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.062

.;T;T;T

MetaRNN

Benign

0.0051

T;T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0050

.;.;.;B

Vest4

0.082

MVP

0.081

MPC

0.014

ClinPred

0.0091

GERP RS

-4.7

gMVP

0.044

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