dbSNP rs112549096: LILRB5:p.Ala556Ser (chr19-54250896-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001081442.3(LILRB5):c.1666G>T(p.Ala556Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,440,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. A556T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

LILRB5
NM_001081442.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

LILRB5 (HGNC:6609): (leukocyte immunoglobulin like receptor B5) 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). Several other LIR subfamily B receptors are expressed on immune cells where they bind to MHC class I molecules on antigen-presenting cells and inhibit stimulation of an immune response. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

LILRB5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1584506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB5	NM_001081442.3 link	c.1666G>T	p.Ala556Ser	missense_variant	Exon 13 of 13	ENST00000449561.3	NP_001074911.2	O75023-3
LILRB5	NM_001304457.3 link	c.1876G>T	p.Ala626Ser	missense_variant	Exon 13 of 13		NP_001291386.2	O75023
LILRB5	NM_006840.5 link	c.1663G>T	p.Ala555Ser	missense_variant	Exon 13 of 13		NP_006831.2	O75023-1
LILRB5	NM_001081443.3 link	c.1366G>T	p.Ala456Ser	missense_variant	Exon 12 of 12		NP_001074912.2	O75023-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB5	ENST00000449561.3 link	c.1666G>T	p.Ala556Ser	missense_variant	Exon 13 of 13	1	NM_001081442.3	ENSP00000406478.1		O75023-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251232

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135840

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1440584

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

716708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000171

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.036

M_CAP

Benign

0.0049

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.055

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Vest4

0.23

MutPred

0.39

Gain of phosphorylation at A555 (P = 0.0528);.;.;

MVP

0.13

MPC

0.29

ClinPred

0.72

GERP RS

-0.70

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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