19-54220579-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006864.4(LILRB3):c.1207A>G(p.Asn403Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000821 in 1,436,998 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N403I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000083 ( 9 hom. )

Consequence

LILRB3
NM_006864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.55

Publications

0 publications found

Variant links:

Genes affected

LILRB3 (HGNC:6607): (leukocyte immunoglobulin like receptor B3) 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]

LILRB3 links:

RPS9 (HGNC:10442): (ribosomal protein S9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS9 links:

LOC124904768 (HGNC:):

LOC124904768 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035161376).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRB3	NM_006864.4	MANE Select	c.1207A>G	p.Asn403Asp	missense	Exon 6 of 13	NP_006855.3	C9JWL8
LILRB3	NM_001320960.2		c.1207A>G	p.Asn403Asp	missense	Exon 6 of 14	NP_001307889.1
LILRB3	NM_001081450.3		c.1207A>G	p.Asn403Asp	missense	Exon 6 of 13	NP_001074919.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRB3	ENST00000445347.2	TSL:2 MANE Select	c.1207A>G	p.Asn403Asp	missense	Exon 6 of 13	ENSP00000388199.2	C9JWL8
LILRB3	ENST00000245620.13	TSL:1	c.1207A>G	p.Asn403Asp	missense	Exon 6 of 13	ENSP00000245620.9	O75022
LILRB3	ENST00000414379.5	TSL:1	n.*714A>G		non_coding_transcript_exon	Exon 7 of 14	ENSP00000416920.1	F8WD89

Frequencies

GnomAD3 genomes

AF:

0.0000709

AC:

AN:

112844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000381

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000831

AC:

110

AN:

1324080

Hom.:

Cov.:

AF XY:

0.0000892

AC XY:

AN XY:

661108

show subpopulations

African (AFR)

AF:

0.000227

AC:

AN:

30790

American (AMR)

AF:

0.000129

AC:

AN:

38838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25348

East Asian (EAS)

AF:

0.00

AC:

AN:

25738

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5312

European-Non Finnish (NFE)

AF:

0.0000871

AC:

AN:

1009886

Other (OTH)

AF:

0.000164

AC:

AN:

54898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.401

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000708

AC:

AN:

112918

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

54634

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000193

AC:

AN:

31122

American (AMR)

AF:

0.00

AC:

AN:

9436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3106

East Asian (EAS)

AF:

0.00

AC:

AN:

2318

South Asian (SAS)

AF:

0.00

AC:

AN:

3692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.0000381

AC:

AN:

52484

Other (OTH)

AF:

0.00

AC:

AN:

1434

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00217160), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.363

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0020

(source)

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.10

M_CAP

Benign

0.0041

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.90

PhyloP100

-5.6

PROVEAN

Benign

-0.69

Sift

Benign

0.56

Sift4G

Benign

0.73

Vest4

0.045

MVP

0.067

ClinPred

0.059

GERP RS

-5.4

gMVP

0.057

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over