rs386056

Positions:

• chr19-54279064-T-C
• chr19-54279064-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080978.4(LILRB2):​c.703A>G​(p.Met235Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 1,605,944 control chromosomes in the GnomAD database, including 510,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.81 (49581 hom., cov: 44)
  • Exomes 𝑓: 0.80 (461412 hom.)
• Consequence: LILRB2 NM_001080978.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029646456).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB2	NM_001080978.4	c.703A>G	p.Met235Val	missense_variant	6/14	ENST00000314446.10	NP_001074447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB2	ENST00000314446.10	c.703A>G	p.Met235Val	missense_variant	6/14	1	NM_001080978.4	ENSP00000319960	A2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 122820 AN: 151358 Hom.: 49543 Cov.: 44

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.898

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.844

GnomAD4 exome AF: 0.797 AC: 1158752 AN: 1454464 Hom.: 461412 Cov.: 145 AF XY: 0.800 AC XY: 578483 AN XY: 723470

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.909

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.838

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.811

Gnomad4 OTH exome AF: 0.806

GnomAD4 genome AF: 0.811 AC: 122919 AN: 151480 Hom.: 49581 Cov.: 44 AF XY: 0.805 AC XY: 59619 AN XY: 74042

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.841

Alfa AF: 0.830 Hom.: 20921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0090
LIST_S2	Benign	0.43	.;.;T;.;.
MetaRNN	Benign	0.0030	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Vest4		0.038
gMVP		0.069

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs386056; hg19: chr19-54782919;