19-54220605-T-A

Variant names:

• chr19-54220605-T-A
• rs763319782
• NM_006864.4:c.1181A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006864.4(LILRB3):​c.1181A>T​(p.Tyr394Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRB3 NM_006864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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]

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]

LOC124904768 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB3	NM_006864.4	c.1181A>T	p.Tyr394Phe	missense_variant	Exon 6 of 13	ENST00000445347.2	NP_006855.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB3	ENST00000445347.2	c.1181A>T	p.Tyr394Phe	missense_variant	Exon 6 of 13	2	NM_006864.4	ENSP00000388199.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000445 AC: 1 AN: 224852 Hom.: 0 AF XY: 0.00000828 AC XY: 1 AN XY: 120760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000145 AC: 2 AN: 1378692 Hom.: 0 Cov.: 74 AF XY: 0.00 AC XY: 0 AN XY: 687230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000361

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ExAC AF: 0.0000256 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1181A>T (p.Y394F) alteration is located in exon 6 (coding exon 6) of the LILRB3 gene. This alteration results from a A to T substitution at nucleotide position 1181, causing the tyrosine (Y) at amino acid position 394 to be replaced by a phenylalanine (F). 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	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.93	.;D;.
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-1.2	T
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Benign	0.28
Sift	Benign	0.041	D;D;D
Sift4G	Uncertain	0.050	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.53
MutPred		0.56		Loss of phosphorylation at Y394 (P = 0.0418);Loss of phosphorylation at Y394 (P = 0.0418);Loss of phosphorylation at Y394 (P = 0.0418);
MVP		0.40
MPC		1.6
ClinPred		0.93	D
GERP RS		2.9
gMVP		0.29

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

Other links and lift over

dbSNP: rs763319782; hg19: chr19-54724475;