19-54632003-C-A

Position:

• chr19-54632003-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/18 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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023768723).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB1	NM_001081637.3	c.427C>A	p.Leu143Ile	missense_variant	5/15	ENST00000324602.12	NP_001075106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB1	ENST00000324602.12	c.427C>A	p.Leu143Ile	missense_variant	5/15	5	NM_001081637.3	ENSP00000315997.7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 53924 AN: 116398 Hom.: 0 Cov.: 41 FAILED QC

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

GnomAD3 exomes AF: 0.0000994 AC: 25 AN: 251456 Hom.: 0 AF XY: 0.0000957 AC XY: 13 AN XY: 135904

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 SAS exome AF: 0.0000653

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.0793

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.0933

Gnomad4 OTH exome AF: 0.177

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

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.471

Alfa AF: 0.0926 Hom.: 0

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.427C>A (p.L143I) alteration is located in exon 5 (coding exon 4) of the LILRB1 gene. This alteration results from a C to A substitution at nucleotide position 427, causing the leucine (L) at amino acid position 143 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.083	T;T;.;.;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.66	T;T;T;T;T;T;.
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.024	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N
REVEL	Benign	0.088
Sift	Benign	0.033	D;D;D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs539532545; hg19: chr19-55143454;