19-54220584-C-T

Variant names:

• chr19-54220584-C-T
• rs752402706
• NM_006864.4:c.1202G>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.1202G>A​(p.Ser401Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. S401R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000025 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRB3 NM_006864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.875
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.072244525).

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.1202G>A	p.Ser401Asn	missense	Exon 6 of 13	NP_006855.3	C9JWL8
	LILRB3	NM_001320960.2		c.1202G>A	p.Ser401Asn	missense	Exon 6 of 14	NP_001307889.1
	LILRB3	NM_001081450.3		c.1202G>A	p.Ser401Asn	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.1202G>A	p.Ser401Asn	missense	Exon 6 of 13	ENSP00000388199.2	C9JWL8
	LILRB3	ENST00000245620.13	TSL:1	c.1202G>A	p.Ser401Asn	missense	Exon 6 of 13	ENSP00000245620.9	O75022
	LILRB3	ENST00000414379.5	TSL:1	n.*709G>A		non_coding_transcript_exon	Exon 7 of 14	ENSP00000416920.1	F8WD89

Frequencies

GnomAD3 genomes AF: 0.0000530 AC: 6 AN: 113248 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000129

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: 0.0000380

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000247 AC: 33 AN: 1336496 Hom.: 1 Cov.: 43 AF XY: 0.0000255 AC XY: 17 AN XY: 667112

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

African (AFR) AF: 0.0000323 AC: 1 AN: 30932

American (AMR) AF: 0.0000510 AC: 2 AN: 39188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25426

East Asian (EAS) AF: 0.00 AC: 0 AN: 25858

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 0.0000284 AC: 29 AN: 1020672

Other (OTH) AF: 0.00 AC: 0 AN: 55372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000530 AC: 6 AN: 113248 Hom.: 0 Cov.: 19 AF XY: 0.000110 AC XY: 6 AN XY: 54786

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

African (AFR) AF: 0.000129 AC: 4 AN: 31128

American (AMR) AF: 0.00 AC: 0 AN: 9480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3118

East Asian (EAS) AF: 0.00 AC: 0 AN: 2338

South Asian (SAS) AF: 0.00 AC: 0 AN: 3718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000380 AC: 2 AN: 52678

Other (OTH) AF: 0.00 AC: 0 AN: 1444

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000824 AC: 10

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	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.7
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.88
PROVEAN	Benign	-1.4	N
Sift	Benign	0.22	T
Sift4G	Benign	0.27	T
Vest4		0.11
MVP		0.092
ClinPred		0.023	T
GERP RS		-2.3
gMVP		0.085

Splicing

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

Other links and lift over

dbSNP: rs752402706; hg19: chr19-54744206;