19-54277919-G-A

Variant names:

• chr19-54277919-G-A
• rs148321423
• NM_001080978.4:c.1279C>T

Variant summary

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

The NM_001080978.4(LILRB2):​c.1279C>T​(p.Pro427Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,539,662 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P427T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: LILRB2 NM_001080978.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.34
• Publications: 3 publications found

Genes affected

LILRB2 (HGNC:6606): (leukocyte immunoglobulin like receptor B2) 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=0.0036373734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080978.4. 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
	LILRB2	NM_001080978.4	MANE Select	c.1279C>T	p.Pro427Ser	missense	Exon 8 of 14	NP_001074447.2	Q8N423-2
	LILRB2	NM_005874.5		c.1279C>T	p.Pro427Ser	missense	Exon 8 of 14	NP_005865.3	Q8N423-1
	LILRB2	NM_001278403.3		c.1279C>T	p.Pro427Ser	missense	Exon 8 of 14	NP_001265332.2	Q8N423-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB2	ENST00000314446.10	TSL:1 MANE Select	c.1279C>T	p.Pro427Ser	missense	Exon 8 of 14	ENSP00000319960.5	Q8N423-2
	LILRB2	ENST00000391749.4	TSL:1	c.1279C>T	p.Pro427Ser	missense	Exon 8 of 14	ENSP00000375629.4	Q8N423-1
	LILRB2	ENST00000391748.5	TSL:1	c.1279C>T	p.Pro427Ser	missense	Exon 8 of 14	ENSP00000375628.1	Q8N423-2

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 279 AN: 152182 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000640 AC: 92 AN: 143816 AF XY: 0.000541

Gnomad AFR exome AF: 0.00808

Gnomad AMR exome AF: 0.000504

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000269

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.000760

GnomAD4 exome AF: 0.000267 AC: 371 AN: 1387362 Hom.: 1 Cov.: 32 AF XY: 0.000246 AC XY: 168 AN XY: 683832

African (AFR) AF: 0.00626 AC: 193 AN: 30840

American (AMR) AF: 0.000483 AC: 16 AN: 33112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24276

East Asian (EAS) AF: 0.00 AC: 0 AN: 35672

South Asian (SAS) AF: 0.0000257 AC: 2 AN: 77828

European-Finnish (FIN) AF: 0.000224 AC: 11 AN: 49092

Middle Eastern (MID) AF: 0.000533 AC: 3 AN: 5626

European-Non Finnish (NFE) AF: 0.0000894 AC: 96 AN: 1073594

Other (OTH) AF: 0.000872 AC: 50 AN: 57322

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152300 Hom.: 1 Cov.: 32 AF XY: 0.00191 AC XY: 142 AN XY: 74466

African (AFR) AF: 0.00626 AC: 260 AN: 41560

American (AMR) AF: 0.000588 AC: 9 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000424 Hom.: 1

Bravo AF: 0.00207

ESP6500AA AF: 0.00457 AC: 19

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000525 AC: 47

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	0.063
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.073
DANN	Benign	0.51
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.015
Sift	Benign	0.50	T
Sift4G	Benign	0.19	T
Vest4		0.17
MVP		0.10
MPC		0.046
ClinPred		0.0026	T
GERP RS		-4.7
gMVP		0.11
Mutation Taster		=97/3	polymorphism

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: rs148321423; hg19: chr19-54781773;