chr19-54636798-G-A

Variant names:

• chr19-54636798-G-A
• rs16985478
• NM_001081637.3:c.1879G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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
• Publications: 18 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: Benign. The variant received -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 VariationId 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.

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.1879G>A	p.Glu627Lys	missense	Exon 15 of 15	NP_001075106.2	A0A087WSV6
	LILRB1	NM_001388358.1		c.1879G>A	p.Glu627Lys	missense	Exon 16 of 16	NP_001375287.1	A0A087WSV6
	LILRB1	NM_001081638.4		c.1876G>A	p.Glu626Lys	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.1879G>A	p.Glu627Lys	missense	Exon 15 of 15	ENSP00000315997.7	A0A087WSV6
	LILRB1	ENST00000396315.5	TSL:1	c.1879G>A	p.Glu627Lys	missense	Exon 14 of 14	ENSP00000379608.1	A0A087WSV6
	LILRB1	ENST00000396327.7	TSL:1	c.1876G>A	p.Glu626Lys	missense	Exon 15 of 15	ENSP00000379618.3	A0A087WSX8

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

GnomAD2 exomes AF: 0.124 AC: 30853 AN: 248112 AF XY: 0.122

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 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

African (AFR) AF: 0.0471 AC: 1460 AN: 31008

American (AMR) AF: 0.161 AC: 7166 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2732 AN: 26100

East Asian (EAS) AF: 0.0881 AC: 3466 AN: 39334

South Asian (SAS) AF: 0.0770 AC: 6207 AN: 80638

European-Finnish (FIN) AF: 0.150 AC: 8036 AN: 53408

Middle Eastern (MID) AF: 0.0583 AC: 330 AN: 5660

European-Non Finnish (NFE) AF: 0.141 AC: 156949 AN: 1110198

Other (OTH) AF: 0.124 AC: 7407 AN: 59714

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

African (AFR) AF: 0.0299 AC: 1168 AN: 39050

American (AMR) AF: 0.158 AC: 2400 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3468

East Asian (EAS) AF: 0.0897 AC: 456 AN: 5086

South Asian (SAS) AF: 0.0582 AC: 257 AN: 4416

European-Finnish (FIN) AF: 0.138 AC: 1454 AN: 10528

Middle Eastern (MID) AF: 0.0828 AC: 24 AN: 290

European-Non Finnish (NFE) AF: 0.137 AC: 9274 AN: 67728

Other (OTH) AF: 0.117 AC: 242 AN: 2074

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.7
DANN	Benign	0.73
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.81
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.012
Sift	Benign	0.62	T
Sift4G	Benign	0.39	T
Polyphen		0.0010	B
Vest4		0.056
MPC		0.063
ClinPred		0.000029	T
GERP RS		-3.6
gMVP		0.041
Mutation Taster		=100/0	polymorphism (auto)

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