19-54636796-G-C

Variant names:

• chr19-54636796-G-C
• rs753349590
• NM_001081637.3:c.1877G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001081637.3(LILRB1):​c.1877G>C​(p.Arg626Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

Genes affected

LILRB1 (HGNC:6605): (leukocyte immunoglobulin like receptor B1) 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]

LILRB1-AS1 (HGNC:53114): (LILRB1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09989345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB1	NM_001081637.3	c.1877G>C	p.Arg626Pro	missense_variant	Exon 15 of 15	ENST00000324602.12	NP_001075106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB1	ENST00000324602.12	c.1877G>C	p.Arg626Pro	missense_variant	Exon 15 of 15	5	NM_001081637.3	ENSP00000315997.7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251474 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461190 Hom.: 0 Cov.: 44 AF XY: 0.00000550 AC XY: 4 AN XY: 726942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 29

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.076	T;T;.;.;T;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;.
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.10	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D
REVEL	Benign	0.051
Sift	Uncertain	0.0030	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D
Polyphen		0.93	.;.;.;.;.;P;.
Vest4		0.22
MutPred		0.19		Gain of glycosylation at R624 (P = 0.0154);.;.;.;.;.;.;
MVP		0.22
MPC		0.31
ClinPred		0.56	D
GERP RS		-2.0
gMVP		0.064

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs753349590; hg19: chr19-55148247;