Variant chr19-54636509-G-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_001081637.3(LILRB1):c.1669G>A(p.Glu557Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,611,270 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

LILRB1
NM_001081637.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.697

Variant links:

Genes affected

LILRB1 (HGNC:6605): (leukocyte immunoglobulin like receptor B1) 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. 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]

LILRB1 links:

LILRB1 (HGNC:):

LILRB1 links:

Genome browser will be placed here

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=0.051705778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB1	NM_001081637.3 linkuse as main transcript	c.1669G>A	p.Glu557Lys	missense_variant	14/15	ENST00000324602.12	NP_001075106.2	Q8NHL6A0A087WSV6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB1	ENST00000324602.12 linkuse as main transcript	c.1669G>A	p.Glu557Lys	missense_variant	14/15	5	NM_001081637.3	ENSP00000315997.7		A0A087WSV6

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

151596

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:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000442

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000301

AC:

AN:

249264

Hom.:

AF XY:

0.000312

AC XY:

AN XY:

134662

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:

0.0000467

Gnomad NFE exome

AF:

0.000640

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000295

AC:

431

AN:

1459674

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

209

AN XY:

726142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

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:

0.0000936

Gnomad4 NFE exome

AF:

0.000372

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000211

AC:

AN:

151596

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

74018

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:

0.0000945

Gnomad4 NFE

AF:

0.000442

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000449

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000412

AC:

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

Oct 26, 2021

The c.1669G>A (p.E557K) alteration is located in exon 14 (coding exon 13) of the LILRB1 gene. This alteration results from a G to A substitution at nucleotide position 1669, causing the glutamic acid (E) at amino acid position 557 to be replaced by a lysine (K). 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

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.031

T;T;.;.;T;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.79

T;T;T;T;T;T;.

M_CAP

Benign

0.00070

MetaRNN

Benign

0.052

T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.88

N;N;N;N;N;N;N

REVEL

Benign

0.045

Sift

Uncertain

0.019

D;D;D;D;D;D;D

Sift4G

Benign

0.40

T;T;T;T;T;T;T

Polyphen

0.46

.;.;.;.;.;P;.

Vest4

0.17

MVP

0.24

MPC

0.14

ClinPred

0.074

GERP RS

1.5

gMVP

0.058

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