rs16985478

Positions:

• chr19-54636798-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001081637.3(LILRB1):​c.1879G>A​(p.Glu627Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,599,308 control chromosomes in the GnomAD database, including 14,274 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (962 hom., cov: 29)
  • Exomes 𝑓: 0.13 (13312 hom.)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.813

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024142861).
• BP6: Variant 19-54636798-G-A is Benign according to our data. Variant chr19-54636798-G-A is described in ClinVar as [Benign]. Clinvar id is 1175563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB1	NM_001081637.3	c.1879G>A	p.Glu627Lys	missense_variant	15/15	ENST00000324602.12	NP_001075106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB1	ENST00000324602.12	c.1879G>A	p.Glu627Lys	missense_variant	15/15	5	NM_001081637.3	ENSP00000315997	P4
LILRB1-AS1	ENST00000456337.1	n.200-722C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 15682 AN: 148574 Hom.: 960 Cov.: 29

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0769

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.124 AC: 30853 AN: 248112 Hom.: 958 AF XY: 0.122 AC XY: 16366 AN XY: 134200

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.0996

Gnomad EAS exome AF: 0.0832

Gnomad SAS exome AF: 0.0911

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.134 AC: 193753 AN: 1450610 Hom.: 13312 Cov.: 44 AF XY: 0.131 AC XY: 94242 AN XY: 720686

Gnomad4 AFR exome AF: 0.0471

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.0881

Gnomad4 SAS exome AF: 0.0770

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.106 AC: 15698 AN: 148698 Hom.: 962 Cov.: 29 AF XY: 0.107 AC XY: 7762 AN XY: 72618

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0943

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.0582

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.117

Alfa AF: 0.119 Hom.: 351

Bravo AF: 0.104

TwinsUK AF: 0.135 AC: 499

ALSPAC AF: 0.147 AC: 567

ExAC AF: 0.130 AC: 15819

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 25855135) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.7
DANN	Benign	0.73
DEOGEN2	Benign	0.014	T;T;.;.;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.65	T;T;T;T;T;T;.
MetaRNN	Benign	0.0024	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.71	N;N;N;N;N;N;N
REVEL	Benign	0.012
Sift	Benign	0.62	T;T;T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T;T
Polyphen		0.0010	.;.;.;.;.;B;.
Vest4		0.056
MPC		0.063
ClinPred		0.000029	T
GERP RS		-3.6
gMVP		0.041

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

Publications

LitVar

Other links and lift over

dbSNP: rs16985478; hg19: chr19-55148249; COSMIC: COSV61115740; COSMIC: COSV61115740;