rs757732370

Variant names:

• chr19-54220579-T-A
• rs757732370
• NM_006864.4:c.1207A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-54220579-T-A
• chr19-54220579-T-C
• chr19-54220579-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006864.4(LILRB3):​c.1207A>T​(p.Asn403Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,437,074 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 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. N403D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000035 (2 hom., cov: 19)
  • Exomes 𝑓: 0.000015 (3 hom.)
• Consequence: LILRB3 NM_006864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.55
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06778222).
• BS2: High Homozygotes in GnomAd4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB3	NM_006864.4	MANE Select	c.1207A>T	p.Asn403Tyr	missense	Exon 6 of 13	NP_006855.3	C9JWL8
	LILRB3	NM_001320960.2		c.1207A>T	p.Asn403Tyr	missense	Exon 6 of 14	NP_001307889.1
	LILRB3	NM_001081450.3		c.1207A>T	p.Asn403Tyr	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.1207A>T	p.Asn403Tyr	missense	Exon 6 of 13	ENSP00000388199.2	C9JWL8
	LILRB3	ENST00000245620.13	TSL:1	c.1207A>T	p.Asn403Tyr	missense	Exon 6 of 13	ENSP00000245620.9	O75022
	LILRB3	ENST00000414379.5	TSL:1	n.*714A>T		non_coding_transcript_exon	Exon 7 of 14	ENSP00000416920.1	F8WD89

Frequencies

GnomAD3 genomes AF: 0.0000354 AC: 4 AN: 112846 Hom.: 2 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000424

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 20 AN: 1324228 Hom.: 3 Cov.: 43 AF XY: 0.00000907 AC XY: 6 AN XY: 661182

African (AFR) AF: 0.00 AC: 0 AN: 30792

American (AMR) AF: 0.000464 AC: 18 AN: 38830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.00 AC: 0 AN: 25738

South Asian (SAS) AF: 0.00 AC: 0 AN: 81464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5314

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1010010

Other (OTH) AF: 0.00 AC: 0 AN: 54902

GnomAD4 genome AF: 0.0000354 AC: 4 AN: 112846 Hom.: 2 Cov.: 19 AF XY: 0.0000733 AC XY: 4 AN XY: 54542

African (AFR) AF: 0.00 AC: 0 AN: 31018

American (AMR) AF: 0.000424 AC: 4 AN: 9434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3106

East Asian (EAS) AF: 0.00 AC: 0 AN: 2324

South Asian (SAS) AF: 0.00 AC: 0 AN: 3694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52492

Other (OTH) AF: 0.00 AC: 0 AN: 1438

Alfa AF: 0.00 Hom.: 0

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	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0020
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.96	T
PhyloP100		-5.6
PROVEAN	Uncertain	-3.4	D
Sift	Benign	0.17	T
Sift4G	Benign	0.16	T
Vest4		0.12
MutPred		0.28		Gain of phosphorylation at N403 (P = 0.0526)
MVP		0.15
ClinPred		0.068	T
GERP RS		-5.4
gMVP		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757732370; hg19: chr19-54744201;