chr19-54280275-C-T

Position:

• chr19-54280275-C-T

Variant summary

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

The NM_001080978.4(LILRB2):​c.59G>A​(p.Arg20His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 1,613,590 control chromosomes in the GnomAD database, including 515,554 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 0.82 (51942 hom., cov: 30)
  • Exomes 𝑓: 0.79 (463612 hom.)
• Consequence: LILRB2 NM_001080978.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.35

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]

LILRB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004478216).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB2	NM_001080978.4	c.59G>A	p.Arg20His	missense_variant	3/14	ENST00000314446.10	NP_001074447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB2	ENST00000314446.10	c.59G>A	p.Arg20His	missense_variant	3/14	1	NM_001080978.4	ENSP00000319960.5

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124488 AN: 151798 Hom.: 51894 Cov.: 30

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.852

GnomAD4 exome AF: 0.790 AC: 1154462 AN: 1461672 Hom.: 463612 Cov.: 126 AF XY: 0.793 AC XY: 576282 AN XY: 727124

Gnomad4 AFR exome AF: 0.912

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.906

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.820 AC: 124598 AN: 151918 Hom.: 51942 Cov.: 30 AF XY: 0.813 AC XY: 60357 AN XY: 74246

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.848

Alfa AF: 0.822 Hom.: 12969

Bravo AF: 0.819

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
LIST_S2	Benign	0.053	.;T;.;.
MetaRNN	Benign	0.0045	T;T;T;T
Sift4G	Benign	0.79	T;T;T;T
Vest4		0.032
gMVP		0.085

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs383369; hg19: chr19-54784130;