NM_001080978.4:c.1198C>G

Variant names:

• chr19-54278320-G-C
• rs528142749
• NM_001080978.4:c.1198C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080978.4(LILRB2):​c.1198C>G​(p.Leu400Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 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: 33)
• Consequence: LILRB2 NM_001080978.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057138443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB2	NM_001080978.4	c.1198C>G	p.Leu400Val	missense_variant	Exon 7 of 14	ENST00000314446.10	NP_001074447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB2	ENST00000314446.10	c.1198C>G	p.Leu400Val	missense_variant	Exon 7 of 14	1	NM_001080978.4	ENSP00000319960.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000189

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	-0.68
CADD	Benign	0.014
DANN	Benign	0.82
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.0040	.;.;T;.;.
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.057	T;T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.47	T;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T
Vest4		0.050
MutPred		0.21		Gain of phosphorylation at Y397 (P = 0.1004);.;Gain of phosphorylation at Y397 (P = 0.1004);Gain of phosphorylation at Y397 (P = 0.1004);Gain of phosphorylation at Y397 (P = 0.1004);
MVP		0.16
MPC		0.048
ClinPred		0.18	T
GERP RS		-0.48
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

LitVar

Other links and lift over

dbSNP: rs528142749; hg19: chr19-54782174;