rs201896387

Variant names:

• chr19-54276882-C-T
• rs201896387
• NM_001080978.4:c.1405G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001080978.4(LILRB2):​c.1405G>A​(p.Val469Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,609,522 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (18 hom.)
• Consequence: LILRB2 NM_001080978.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.36
• Publications: 5 publications found

Genes affected

LILRB2 (HGNC:6606): (leukocyte immunoglobulin like receptor B2) 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008268654).
• BP6: Variant 19-54276882-C-T is Benign according to our data. Variant chr19-54276882-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080978.4. 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
	LILRB2	NM_001080978.4	MANE Select	c.1405G>A	p.Val469Ile	missense	Exon 10 of 14	NP_001074447.2	Q8N423-2
	LILRB2	NM_005874.5		c.1408G>A	p.Val470Ile	missense	Exon 10 of 14	NP_005865.3	Q8N423-1
	LILRB2	NM_001278403.3		c.1405G>A	p.Val469Ile	missense	Exon 10 of 14	NP_001265332.2	Q8N423-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB2	ENST00000314446.10	TSL:1 MANE Select	c.1405G>A	p.Val469Ile	missense	Exon 10 of 14	ENSP00000319960.5	Q8N423-2
	LILRB2	ENST00000391749.4	TSL:1	c.1408G>A	p.Val470Ile	missense	Exon 10 of 14	ENSP00000375629.4	Q8N423-1
	LILRB2	ENST00000391748.5	TSL:1	c.1405G>A	p.Val469Ile	missense	Exon 10 of 14	ENSP00000375628.1	Q8N423-2

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 570 AN: 151732 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00500

Gnomad OTH AF: 0.00385

GnomAD2 exomes AF: 0.00224 AC: 555 AN: 247552 AF XY: 0.00256

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00716

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.000744

Gnomad NFE exome AF: 0.00145

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00215 AC: 3136 AN: 1457672 Hom.: 18 Cov.: 32 AF XY: 0.00243 AC XY: 1761 AN XY: 724938

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

African (AFR) AF: 0.000599 AC: 20 AN: 33416

American (AMR) AF: 0.000268 AC: 12 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00927 AC: 239 AN: 25790

East Asian (EAS) AF: 0.00128 AC: 51 AN: 39690

South Asian (SAS) AF: 0.00904 AC: 771 AN: 85242

European-Finnish (FIN) AF: 0.00278 AC: 148 AN: 53254

Middle Eastern (MID) AF: 0.00574 AC: 33 AN: 5746

European-Non Finnish (NFE) AF: 0.00153 AC: 1698 AN: 1109686

Other (OTH) AF: 0.00273 AC: 164 AN: 60146

⚠️ 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: 0.00376 AC: 571 AN: 151850 Hom.: 4 Cov.: 31 AF XY: 0.00373 AC XY: 277 AN XY: 74234

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

African (AFR) AF: 0.000917 AC: 38 AN: 41420

American (AMR) AF: 0.000524 AC: 8 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 51 AN: 3452

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.0128 AC: 61 AN: 4764

European-Finnish (FIN) AF: 0.00537 AC: 57 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00500 AC: 339 AN: 67850

Other (OTH) AF: 0.00381 AC: 8 AN: 2098

⚠️ 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: 0.00638 Hom.: 6

ExAC AF: 0.00445 AC: 540

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.031
DANN	Benign	0.33
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00069	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.94	T
PhyloP100		-3.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.022
Sift	Benign	0.41	T
Sift4G	Benign	0.51	T
Vest4		0.17
MVP		0.048
MPC		0.040
ClinPred		0.011	T
GERP RS		-3.0
gMVP		0.071
Mutation Taster		=100/0	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: rs201896387; hg19: chr19-54780736; COSMIC: COSV106100024; COSMIC: COSV106100024;