rs539532545

Variant names:

• chr19-54632003-C-A
• rs539532545
• NM_001081637.3:c.427C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54632003-C-A
• chr19-54632003-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001081637.3(LILRB1):​c.427C>A​(p.Leu143Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,158,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.46 (0 hom., cov: 41)
  • Exomes 𝑓: 0.12 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.481
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the MID (0.29) population. However there is too low homozygotes in high coverage region: (expected more than 4155, got 0).
• BP4: Computational evidence support a benign effect (MetaRNN=0.023768723).

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.427C>A	p.Leu143Ile	missense	Exon 5 of 15	NP_001075106.2	A0A087WSV6
	LILRB1	NM_001388358.1		c.427C>A	p.Leu143Ile	missense	Exon 6 of 16	NP_001375287.1	A0A087WSV6
	LILRB1	NM_001081638.4		c.427C>A	p.Leu143Ile	missense	Exon 5 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.427C>A	p.Leu143Ile	missense	Exon 5 of 15	ENSP00000315997.7	A0A087WSV6
	LILRB1	ENST00000396315.5	TSL:1	c.427C>A	p.Leu143Ile	missense	Exon 4 of 14	ENSP00000379608.1	A0A087WSV6
	LILRB1	ENST00000396327.7	TSL:1	c.427C>A	p.Leu143Ile	missense	Exon 5 of 15	ENSP00000379618.3	A0A087WSX8

Frequencies

GnomAD3 genomes AF: 0.463 AC: 53924 AN: 116398 Hom.: 0 Cov.: 41

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.485

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.471

GnomAD2 exomes AF: 0.0000994 AC: 25 AN: 251456 AF XY: 0.0000957

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.120 AC: 138777 AN: 1158596 Hom.: 0 Cov.: 112 AF XY: 0.130 AC XY: 74471 AN XY: 572158

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

African (AFR) AF: 0.200 AC: 4636 AN: 23202

American (AMR) AF: 0.156 AC: 4494 AN: 28772

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 5253 AN: 19160

East Asian (EAS) AF: 0.0793 AC: 2107 AN: 26576

South Asian (SAS) AF: 0.244 AC: 15049 AN: 61612

European-Finnish (FIN) AF: 0.336 AC: 12635 AN: 37598

Middle Eastern (MID) AF: 0.304 AC: 1434 AN: 4724

European-Non Finnish (NFE) AF: 0.0933 AC: 85073 AN: 911336

Other (OTH) AF: 0.177 AC: 8096 AN: 45616

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.463 AC: 53964 AN: 116474 Hom.: 0 Cov.: 41 AF XY: 0.461 AC XY: 26127 AN XY: 56710

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

African (AFR) AF: 0.490 AC: 16808 AN: 34312

American (AMR) AF: 0.453 AC: 5213 AN: 11508

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1408 AN: 2854

East Asian (EAS) AF: 0.261 AC: 959 AN: 3670

South Asian (SAS) AF: 0.471 AC: 1736 AN: 3686

European-Finnish (FIN) AF: 0.434 AC: 3358 AN: 7740

Middle Eastern (MID) AF: 0.484 AC: 119 AN: 246

European-Non Finnish (NFE) AF: 0.464 AC: 23241 AN: 50102

Other (OTH) AF: 0.471 AC: 753 AN: 1600

⚠️ 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: 0.0926 Hom.: 0

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.48
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.088
Sift	Benign	0.033	D
Sift4G	Uncertain	0.013	D
Polyphen		0.72	P
Vest4		0.21
MVP		0.088
MPC		0.14
ClinPred		0.091	T
GERP RS		-2.4
gMVP		0.041
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs539532545; hg19: chr19-55143454;