rs745357082

Variant names:

• chr19-54631695-C-T
• rs745357082
• NM_001081637.3:c.266C>T

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.266C>T​(p.Thr89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 56)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.92
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20848995).

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.266C>T	p.Thr89Ile	missense	Exon 4 of 15	NP_001075106.2	A0A087WSV6
	LILRB1	NM_001388358.1		c.266C>T	p.Thr89Ile	missense	Exon 5 of 16	NP_001375287.1	A0A087WSV6
	LILRB1	NM_001081638.4		c.266C>T	p.Thr89Ile	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.266C>T	p.Thr89Ile	missense	Exon 4 of 15	ENSP00000315997.7	A0A087WSV6
	LILRB1	ENST00000396315.5	TSL:1	c.266C>T	p.Thr89Ile	missense	Exon 3 of 14	ENSP00000379608.1	A0A087WSV6
	LILRB1	ENST00000396327.7	TSL:1	c.266C>T	p.Thr89Ile	missense	Exon 4 of 15	ENSP00000379618.3	A0A087WSX8

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152288 Hom.: 0 Cov.: 56

Gnomad AFR AF: 0.000121

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251466 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461880 Hom.: 0 Cov.: 140 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152288 Hom.: 0 Cov.: 56 AF XY: 0.0000269 AC XY: 2 AN XY: 74400

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000121 AC: 5 AN: 41484

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.29
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.9
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.040
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.042	D
Polyphen		0.98	D
Vest4		0.18
MutPred		0.59		Gain of MoRF binding (P = 0.2865)
MVP		0.48
MPC		0.093
ClinPred		0.47	T
GERP RS		-0.65
gMVP		0.16
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs745357082; hg19: chr19-55143146;