19-54219161-A-T

Variant names:

• chr19-54219161-A-T
• rs61734493
• NM_006864.4:c.1394T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006864.4(LILRB3):​c.1394T>A​(p.Leu465His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 1,606,912 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000055 (1 hom.)
• Consequence: LILRB3 NM_006864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0930

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]

LOC124904768 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1704818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB3	NM_006864.4	c.1394T>A	p.Leu465His	missense_variant	Exon 8 of 13	ENST00000445347.2	NP_006855.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB3	ENST00000445347.2	c.1394T>A	p.Leu465His	missense_variant	Exon 8 of 13	2	NM_006864.4	ENSP00000388199.2

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151400 Hom.: 0 Cov.: 27

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: 0.000838

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000550 AC: 80 AN: 1455394 Hom.: 1 Cov.: 59 AF XY: 0.0000718 AC XY: 52 AN XY: 724400

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33002

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 43096

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25762

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39674

Gnomad4 SAS exome AF: 0.000675 AC: 58 AN: 85956

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53166

Gnomad4 NFE exome AF: 0.0000135 AC: 15 AN: 1108966

Gnomad4 Remaining exome AF: 0.0000999 AC: 6 AN: 60052

GnomAD4 genome AF: 0.0000396 AC: 6 AN: 151518 Hom.: 0 Cov.: 27 AF XY: 0.0000676 AC XY: 5 AN XY: 73948

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000839 AC: 0.000838574 AN: 0.000838574

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000295 AC: 0.0000294837 AN: 0.0000294837

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00 Hom.: 31931

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1394G>A (p.R465Q) alteration is located in exon 8 (coding exon 8) of the LILRB3 gene. This alteration results from a G to A substitution at nucleotide position 1394, causing the arginine (R) at amino acid position 465 to be replaced by a glutamine (Q). 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_noAF	Benign	-0.78
CADD	Benign	5.4
LIST_S2	Benign	0.080	.;T;.
MetaRNN	Benign	0.17	T;T;T
Sift4G	Benign	0.54	T;T;T
Vest4		0.32
gMVP		0.15
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs61734493; hg19: chr19-54723030;