rs200859502

Variant names:

• chr19-54632205-T-C
• rs200859502
• NM_001081637.3:c.629T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001081637.3(LILRB1):​c.629T>C​(p.Leu210Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000505 in 1,613,732 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 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (0 hom.)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.48
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027337074).

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.629T>C	p.Leu210Pro	missense	Exon 5 of 15	NP_001075106.2	A0A087WSV6
	LILRB1	NM_001388358.1		c.629T>C	p.Leu210Pro	missense	Exon 6 of 16	NP_001375287.1	A0A087WSV6
	LILRB1	NM_001081638.4		c.629T>C	p.Leu210Pro	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.629T>C	p.Leu210Pro	missense	Exon 5 of 15	ENSP00000315997.7	A0A087WSV6
	LILRB1	ENST00000396315.5	TSL:1	c.629T>C	p.Leu210Pro	missense	Exon 4 of 14	ENSP00000379608.1	A0A087WSV6
	LILRB1	ENST00000396327.7	TSL:1	c.629T>C	p.Leu210Pro	missense	Exon 5 of 15	ENSP00000379618.3	A0A087WSX8

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.000529

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000191 AC: 48 AN: 250994 AF XY: 0.000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000379

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000529 AC: 773 AN: 1461570 Hom.: 0 Cov.: 87 AF XY: 0.000545 AC XY: 396 AN XY: 727038

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.000671 AC: 746 AN: 1111750

Other (OTH) AF: 0.000381 AC: 23 AN: 60374

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74326

African (AFR) AF: 0.0000724 AC: 3 AN: 41434

American (AMR) AF: 0.000196 AC: 3 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000359 Hom.: 0

Bravo AF: 0.000295

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.000436

EpiControl AF: 0.000296

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	0.14
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.043
DANN	Benign	0.38
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
PhyloP100		-7.5
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.072
Sift	Benign	0.26	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.057
MVP		0.040
MPC		0.087
ClinPred		0.068	T
GERP RS		-3.1
gMVP		0.15
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs200859502; hg19: chr19-55143656;