Variant 19-54663046-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001278426.4(LILRB4):c.13T>A(p.Phe5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F5L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LILRB4
NM_001278426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0990

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 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=0.05234617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB4	NM_001278426.4 linkuse as main transcript	c.13T>A	p.Phe5Ile	missense_variant	1/12	ENST00000695418.1	NP_001265355.2	Q8NHJ6A0A8Q3SHR1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB4	ENST00000695418.1 linkuse as main transcript	c.13T>A	p.Phe5Ile	missense_variant	1/12		NM_001278426.4	ENSP00000511897.1		A0A8Q3SHR1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250870

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135596

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:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.9

DANN

Benign

0.91

DEOGEN2

Benign

0.010

.;.;T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.51

T;.;T;T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.052

T;T;T;T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.32

PROVEAN

Benign

1.4

.;N;N;N;N;N

REVEL

Benign

0.038

Sift

Uncertain

0.026

.;D;D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D;D;D

Polyphen

0.15, 0.35

.;.;.;B;.;B

Vest4

0.25, 0.27, 0.26, 0.28

MutPred

0.32

.;Gain of catalytic residue at F5 (P = 0.0617);Gain of catalytic residue at F5 (P = 0.0617);Gain of catalytic residue at F5 (P = 0.0617);Gain of catalytic residue at F5 (P = 0.0617);Gain of catalytic residue at F5 (P = 0.0617);

MVP

0.048

MPC

0.015

ClinPred

0.056

GERP RS

0.48

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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