rs763319782

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-54220605-T-A
• chr19-54220605-T-C
• chr19-54220605-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB3	NM_006864.4	MANE Select	c.1181A>T	p.Tyr394Phe	missense	Exon 6 of 13	NP_006855.3	C9JWL8
	LILRB3	NM_001320960.2		c.1181A>T	p.Tyr394Phe	missense	Exon 6 of 14	NP_001307889.1
	LILRB3	NM_001081450.3		c.1181A>T	p.Tyr394Phe	missense	Exon 6 of 13	NP_001074919.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB3	ENST00000445347.2	TSL:2 MANE Select	c.1181A>T	p.Tyr394Phe	missense	Exon 6 of 13	ENSP00000388199.2	C9JWL8
	LILRB3	ENST00000245620.13	TSL:1	c.1181A>T	p.Tyr394Phe	missense	Exon 6 of 13	ENSP00000245620.9	O75022
	LILRB3	ENST00000414379.5	TSL:1	n.*688A>T		non_coding_transcript_exon	Exon 7 of 14	ENSP00000416920.1	F8WD89

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000445 AC: 1 AN: 224852 AF XY: 0.00000828

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 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

African (AFR) AF: 0.00 AC: 0 AN: 31558

American (AMR) AF: 0.00 AC: 0 AN: 40660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.0000361 AC: 1 AN: 27664

South Asian (SAS) AF: 0.00 AC: 0 AN: 82954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52588

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054998

Other (OTH) AF: 0.00 AC: 0 AN: 56972

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000256 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
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
MetaSVM	Benign	-1.2	T
PhyloP100		1.7
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.28
Sift	Benign	0.041	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.56		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
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs763319782; hg19: chr19-54724475;