rs386056

Variant names:

• chr19-54279064-T-C
• rs386056
• NM_001080978.4:c.703A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 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 0.81 (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
• Publications: 37 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=0.0029646456).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 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.703A>G	p.Met235Val	missense	Exon 6 of 14	NP_001074447.2	Q8N423-2
	LILRB2	NM_005874.5		c.703A>G	p.Met235Val	missense	Exon 6 of 14	NP_005865.3	Q8N423-1
	LILRB2	NM_001278403.3		c.703A>G	p.Met235Val	missense	Exon 6 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.703A>G	p.Met235Val	missense	Exon 6 of 14	ENSP00000319960.5	Q8N423-2
	LILRB2	ENST00000391749.4	TSL:1	c.703A>G	p.Met235Val	missense	Exon 6 of 14	ENSP00000375629.4	Q8N423-1
	LILRB2	ENST00000391748.5	TSL:1	c.703A>G	p.Met235Val	missense	Exon 6 of 14	ENSP00000375628.1	Q8N423-2

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

African (AFR) AF: 0.858 AC: 28640 AN: 33374

American (AMR) AF: 0.681 AC: 30145 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 23731 AN: 26094

East Asian (EAS) AF: 0.320 AC: 11645 AN: 36384

South Asian (SAS) AF: 0.838 AC: 71962 AN: 85840

European-Finnish (FIN) AF: 0.735 AC: 38983 AN: 53058

Middle Eastern (MID) AF: 0.907 AC: 5217 AN: 5752

European-Non Finnish (NFE) AF: 0.811 AC: 900045 AN: 1109628

Other (OTH) AF: 0.806 AC: 48384 AN: 60064

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

African (AFR) AF: 0.859 AC: 35586 AN: 41416

American (AMR) AF: 0.785 AC: 11971 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3151 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2086 AN: 4912

South Asian (SAS) AF: 0.825 AC: 3972 AN: 4816

European-Finnish (FIN) AF: 0.735 AC: 7731 AN: 10522

Middle Eastern (MID) AF: 0.897 AC: 262 AN: 292

European-Non Finnish (NFE) AF: 0.820 AC: 55568 AN: 67782

Other (OTH) AF: 0.841 AC: 1777 AN: 2112

Alfa AF: 0.830 Hom.: 20921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0090
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0030	T
PhyloP100		-1.2
Sift4G	Benign	1.0	T
Vest4		0.038
gMVP		0.069

Splicing

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

Other links and lift over

dbSNP: rs386056; hg19: chr19-54782919;