dbSNP rs386056: LILRB2:p.Met235Val (chr19-54279064-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080978.4(LILRB2):c.703A>G(p.Met235Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 1,605,944 control chromosomes in the GnomAD database, including 510,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.81 ( 49581 hom., cov: 44)

Exomes 𝑓: 0.80 ( 461412 hom. )

Consequence

LILRB2
NM_001080978.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

37 publications found

Variant links:

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]

LILRB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029646456).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRB2	NM_001080978.4 link	c.703A>G	p.Met235Val	missense_variant	Exon 6 of 14	ENST00000314446.10	NP_001074447.2	Q8N423-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRB2	ENST00000314446.10 link	c.703A>G	p.Met235Val	missense_variant	Exon 6 of 14	1	NM_001080978.4	ENSP00000319960.5		Q8N423-2

Frequencies

GnomAD3 genomes

AF:

0.811

AC:

122820

AN:

151358

Hom.:

49543

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.896

Gnomad AMR

AF:

0.785

Gnomad ASJ

AF:

0.908

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.898

Gnomad NFE

AF:

0.820

Gnomad OTH

AF:

0.844

GnomAD4 exome

AF:

0.797

AC:

1158752

AN:

1454464

Hom.:

461412

Cov.:

145

AF XY:

0.800

AC XY:

578483

AN XY:

723470

show subpopulations

African (AFR)

AF:

0.858

AC:

28640

AN:

33374

American (AMR)

AF:

0.681

AC:

30145

AN:

44270

Ashkenazi Jewish (ASJ)

AF:

0.909

AC:

23731

AN:

26094

East Asian (EAS)

AF:

0.320

AC:

11645

AN:

36384

South Asian (SAS)

AF:

0.838

AC:

71962

AN:

85840

European-Finnish (FIN)

AF:

0.735

AC:

38983

AN:

53058

Middle Eastern (MID)

AF:

0.907

AC:

5217

AN:

5752

European-Non Finnish (NFE)

AF:

0.811

AC:

900045

AN:

1109628

Other (OTH)

AF:

0.806

AC:

48384

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.626

Heterozygous variant carriers

14335

28670

43006

57341

71676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20890

41780

62670

83560

104450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.811

AC:

122919

AN:

151480

Hom.:

49581

Cov.:

AF XY:

0.805

AC XY:

59619

AN XY:

74042

show subpopulations

African (AFR)

AF:

0.859

AC:

35586

AN:

41416

American (AMR)

AF:

0.785

AC:

11971

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.908

AC:

3151

AN:

3470

East Asian (EAS)

AF:

0.425

AC:

2086

AN:

4912

South Asian (SAS)

AF:

0.825

AC:

3972

AN:

4816

European-Finnish (FIN)

AF:

0.735

AC:

7731

AN:

10522

Middle Eastern (MID)

AF:

0.897

AC:

262

AN:

292

European-Non Finnish (NFE)

AF:

0.820

AC:

55568

AN:

67782

Other (OTH)

AF:

0.841

AC:

1777

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.616

Heterozygous variant carriers

1171

2342

3513

4684

5855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.830

Hom.:

20921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0090

(source)

LIST_S2

Benign

0.43

.;.;T;.;.

MetaRNN

Benign

0.0030

T;T;T;T;T

PhyloP100

-1.2

Sift4G

Benign

1.0

T;T;T;T;T

Vest4

0.038

gMVP

0.069

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over