19-54280275-C-T

Variant names:

• chr19-54280275-C-T
• rs383369
• NM_001080978.4:c.59G>A

Variant summary

Our verdict is Benign. The variant received -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. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 34 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 -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.

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.59G>A	p.Arg20His	missense	Exon 3 of 14	NP_001074447.2	Q8N423-2
	LILRB2	NM_005874.5		c.59G>A	p.Arg20His	missense	Exon 3 of 14	NP_005865.3	Q8N423-1
	LILRB2	NM_001278403.3		c.59G>A	p.Arg20His	missense	Exon 3 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.59G>A	p.Arg20His	missense	Exon 3 of 14	ENSP00000319960.5	Q8N423-2
	LILRB2	ENST00000391749.4	TSL:1	c.59G>A	p.Arg20His	missense	Exon 3 of 14	ENSP00000375629.4	Q8N423-1
	LILRB2	ENST00000391748.5	TSL:1	c.59G>A	p.Arg20His	missense	Exon 3 of 14	ENSP00000375628.1	Q8N423-2

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

African (AFR) AF: 0.912 AC: 30541 AN: 33478

American (AMR) AF: 0.673 AC: 30105 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 23688 AN: 26134

East Asian (EAS) AF: 0.267 AC: 10582 AN: 39696

South Asian (SAS) AF: 0.831 AC: 71669 AN: 86250

European-Finnish (FIN) AF: 0.728 AC: 38864 AN: 53394

Middle Eastern (MID) AF: 0.905 AC: 5164 AN: 5704

European-Non Finnish (NFE) AF: 0.805 AC: 895443 AN: 1111918

Other (OTH) AF: 0.802 AC: 48406 AN: 60382

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

African (AFR) AF: 0.912 AC: 37811 AN: 41464

American (AMR) AF: 0.785 AC: 11994 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3146 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1875 AN: 5084

South Asian (SAS) AF: 0.818 AC: 3936 AN: 4812

European-Finnish (FIN) AF: 0.725 AC: 7668 AN: 10572

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55306 AN: 67924

Other (OTH) AF: 0.848 AC: 1785 AN: 2106

Alfa AF: 0.822 Hom.: 12969

Bravo AF: 0.819

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
LIST_S2	Benign	0.053	T
MetaRNN	Benign	0.0045	T
PhyloP100		-6.4
Sift4G	Benign	0.79	T
Vest4		0.032
PromoterAI		-0.053	Neutral
gMVP		0.085

Splicing

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

Other links and lift over

dbSNP: rs383369; hg19: chr19-54784130;