NM_001081637.3:c.1853A>G

Variant names:

• chr19-54636772-A-G
• rs746914203
• NM_001081637.3:c.1853A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001081637.3(LILRB1):​c.1853A>G​(p.Gln618Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,571,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.654
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15593287).

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.1853A>G	p.Gln618Arg	missense	Exon 15 of 15	NP_001075106.2	A0A087WSV6
	LILRB1	NM_001388358.1		c.1853A>G	p.Gln618Arg	missense	Exon 16 of 16	NP_001375287.1	A0A087WSV6
	LILRB1	NM_001081638.4		c.1850A>G	p.Gln617Arg	missense	Exon 15 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.1853A>G	p.Gln618Arg	missense	Exon 15 of 15	ENSP00000315997.7	A0A087WSV6
	LILRB1	ENST00000396315.5	TSL:1	c.1853A>G	p.Gln618Arg	missense	Exon 14 of 14	ENSP00000379608.1	A0A087WSV6
	LILRB1	ENST00000396327.7	TSL:1	c.1850A>G	p.Gln617Arg	missense	Exon 15 of 15	ENSP00000379618.3	A0A087WSX8

Frequencies

GnomAD3 genomes AF: 0.00000717 AC: 1 AN: 139422 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251466 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000119 AC: 17 AN: 1431668 Hom.: 0 Cov.: 41 AF XY: 0.0000126 AC XY: 9 AN XY: 712184

African (AFR) AF: 0.0000308 AC: 1 AN: 32516

American (AMR) AF: 0.000114 AC: 5 AN: 43682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24974

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36868

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50972

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5604

European-Non Finnish (NFE) AF: 0.00000732 AC: 8 AN: 1092738

Other (OTH) AF: 0.00 AC: 0 AN: 58262

GnomAD4 genome AF: 0.00000717 AC: 1 AN: 139554 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 66976

African (AFR) AF: 0.00 AC: 0 AN: 38096

American (AMR) AF: 0.00 AC: 0 AN: 12452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65888

Other (OTH) AF: 0.00 AC: 0 AN: 1962

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000576 AC: 7

ClinVar

ClinVar submissions

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	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.65
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.47		Gain of MoRF binding (P = 0.056)
MVP		0.25
MPC		0.34
ClinPred		0.23	T
GERP RS		1.8
gMVP		0.064
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs746914203; hg19: chr19-55148223;