rs988504832

Variant names:

• chr19-54631566-C-A
• rs988504832
• NM_001081637.3:c.137C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001081637.3(LILRB1):​c.137C>A​(p.Thr46Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 47)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.795
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081637.3. 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
	LILRB1	NM_001081637.3	MANE Select	c.137C>A	p.Thr46Asn	missense	Exon 4 of 15	NP_001075106.2	A0A087WSV6
	LILRB1	NM_001388358.1		c.137C>A	p.Thr46Asn	missense	Exon 5 of 16	NP_001375287.1	A0A087WSV6
	LILRB1	NM_001081638.4		c.137C>A	p.Thr46Asn	missense	Exon 4 of 15	NP_001075107.2	A0A087WSX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB1	ENST00000324602.12	TSL:5 MANE Select	c.137C>A	p.Thr46Asn	missense	Exon 4 of 15	ENSP00000315997.7	A0A087WSV6
	LILRB1	ENST00000396315.5	TSL:1	c.137C>A	p.Thr46Asn	missense	Exon 3 of 14	ENSP00000379608.1	A0A087WSV6
	LILRB1	ENST00000396327.7	TSL:1	c.137C>A	p.Thr46Asn	missense	Exon 4 of 15	ENSP00000379618.3	A0A087WSX8

Frequencies

GnomAD3 genomes Cov.: 47

GnomAD4 exome Cov.: 123

GnomAD4 genome Cov.: 47

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.00063	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.80
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.040
Sift	Benign	0.056	T
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.61		Gain of sheet (P = 0.0827)
MVP		0.52
MPC		0.35
ClinPred		0.82	D
GERP RS		0.94
PromoterAI		-0.034	Neutral
gMVP		0.26
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs988504832; hg19: chr19-55143017;