19-54631976-G-C

Variant names:

• chr19-54631976-G-C
• NM_001081637.3:c.400G>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.400G>C​(p.Val134Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,742 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: 44)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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]

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=0.09887043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB1	NM_001081637.3	c.400G>C	p.Val134Leu	missense_variant	Exon 5 of 15	ENST00000324602.12	NP_001075106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB1	ENST00000324602.12	c.400G>C	p.Val134Leu	missense_variant	Exon 5 of 15	5	NM_001081637.3	ENSP00000315997.7

Frequencies

GnomAD3 genomes Cov.: 44

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461742 Hom.: 0 Cov.: 101 AF XY: 0.00000275 AC XY: 2 AN XY: 727168

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: 0.00

GnomAD4 genome Cov.: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.10	T;T;.;.;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.75	T;T;T;T;T;T;.
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.099	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D;D
REVEL	Benign	0.019
Sift	Uncertain	0.020	D;D;D;D;D;D;D
Sift4G	Benign	0.096	T;T;T;T;T;T;T
Polyphen		0.10	.;.;.;.;.;B;.
Vest4		0.043
MutPred		0.68		Gain of glycosylation at P133 (P = 0.1699);Gain of glycosylation at P133 (P = 0.1699);Gain of glycosylation at P133 (P = 0.1699);Gain of glycosylation at P133 (P = 0.1699);.;Gain of glycosylation at P133 (P = 0.1699);Gain of glycosylation at P133 (P = 0.1699);
MVP		0.076
MPC		0.061
ClinPred		0.15	T
GERP RS		-0.89
gMVP		0.038

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55143427;