NM_001081637.3:c.530C>T

Variant names:

• chr19-54632106-C-T
• rs760073992
• NM_001081637.3:c.530C>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.530C>T​(p.Ser177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,128 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 0.000033 (0 hom., cov: 41)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: LILRB1 NM_001081637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.11
• Publications: 3 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: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049684256).

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.530C>T	p.Ser177Leu	missense	Exon 5 of 15	NP_001075106.2	A0A087WSV6
	LILRB1	NM_001388358.1		c.530C>T	p.Ser177Leu	missense	Exon 6 of 16	NP_001375287.1	A0A087WSV6
	LILRB1	NM_001081638.4		c.530C>T	p.Ser177Leu	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.530C>T	p.Ser177Leu	missense	Exon 5 of 15	ENSP00000315997.7	A0A087WSV6
	LILRB1	ENST00000396315.5	TSL:1	c.530C>T	p.Ser177Leu	missense	Exon 4 of 14	ENSP00000379608.1	A0A087WSV6
	LILRB1	ENST00000396327.7	TSL:1	c.530C>T	p.Ser177Leu	missense	Exon 5 of 15	ENSP00000379618.3	A0A087WSX8

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152254 Hom.: 0 Cov.: 41

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251482 AF XY: 0.0000368

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1461874 Hom.: 0 Cov.: 163 AF XY: 0.0000344 AC XY: 25 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111994

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152254 Hom.: 0 Cov.: 41 AF XY: 0.0000134 AC XY: 1 AN XY: 74384

African (AFR) AF: 0.0000241 AC: 1 AN: 41476

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.0000710 Hom.: 0

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

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	-0.47	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.016
DANN	Benign	0.80
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.98	T
PhyloP100		-2.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.0060
Sift	Benign	0.20	T
Sift4G	Benign	0.67	T
Polyphen		0.025	B
Vest4		0.050
MutPred		0.32		Loss of disorder (P = 0.0053)
MVP		0.061
MPC		0.052
ClinPred		0.025	T
GERP RS		-0.79
gMVP		0.073
Mutation Taster		=99/1	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: rs760073992; hg19: chr19-55143557; COSMIC: COSV61121914; COSMIC: COSV61121914;