NM_001080978.4:c.1222T>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080978.4(LILRB2):c.1222T>A(p.Ser408Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,450,686 control chromosomes in the GnomAD database, including 3 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

LILRB2
NM_001080978.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.168

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028005987).

BP6

Variant 19-54278296-A-T is Benign according to our data. Variant chr19-54278296-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2364161.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRB2	NM_001080978.4	MANE Select	c.1222T>A	p.Ser408Thr	missense	Exon 7 of 14	NP_001074447.2	Q8N423-2
LILRB2	NM_005874.5		c.1222T>A	p.Ser408Thr	missense	Exon 7 of 14	NP_005865.3	Q8N423-1
LILRB2	NM_001278403.3		c.1222T>A	p.Ser408Thr	missense	Exon 7 of 14	NP_001265332.2	Q8N423-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LILRB2	ENST00000314446.10	TSL:1 MANE Select	c.1222T>A	p.Ser408Thr	missense	Exon 7 of 14	ENSP00000319960.5	Q8N423-2
LILRB2	ENST00000391749.4	TSL:1	c.1222T>A	p.Ser408Thr	missense	Exon 7 of 14	ENSP00000375629.4	Q8N423-1
LILRB2	ENST00000391748.5	TSL:1	c.1222T>A	p.Ser408Thr	missense	Exon 7 of 14	ENSP00000375628.1	Q8N423-2

Frequencies

GnomAD3 genomes

AF:

0.000597

AC:

AN:

137274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000364

Gnomad ASJ

AF:

0.000318

Gnomad EAS

AF:

0.00222

Gnomad SAS

AF:

0.000956

Gnomad FIN

AF:

0.000522

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000239

Gnomad OTH

AF:

0.00209

GnomAD2 exomes

AF:

0.000286

AC:

AN:

251442

AF XY:

0.000287

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000652

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000420

AC:

610

AN:

1450686

Hom.:

Cov.:

AF XY:

0.000439

AC XY:

317

AN XY:

721530

show subpopulations

African (AFR)

AF:

0.000340

AC:

AN:

32358

American (AMR)

AF:

0.000522

AC:

AN:

44066

Ashkenazi Jewish (ASJ)

AF:

0.0000779

AC:

AN:

25682

East Asian (EAS)

AF:

0.00714

AC:

280

AN:

39236

South Asian (SAS)

AF:

0.000754

AC:

AN:

84884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53156

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000183

AC:

202

AN:

1105822

Other (OTH)

AF:

0.000435

AC:

AN:

59762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

131

175

219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000612

AC:

AN:

137352

Hom.:

Cov.:

AF XY:

0.000747

AC XY:

AN XY:

66942

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00106

AC:

AN:

35930

American (AMR)

AF:

0.000364

AC:

AN:

13746

Ashkenazi Jewish (ASJ)

AF:

0.000318

AC:

AN:

3144

East Asian (EAS)

AF:

0.00223

AC:

AN:

4936

South Asian (SAS)

AF:

0.00120

AC:

AN:

4174

European-Finnish (FIN)

AF:

0.000522

AC:

AN:

9582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.000239

AC:

AN:

62802

Other (OTH)

AF:

0.00206

AC:

AN:

1942

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000444089), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000329

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.4

(source)

DANN

Benign

0.63

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.68

M_CAP

Benign

0.0029

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.99

PhyloP100

0.17

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.0

REVEL

Benign

0.051

Sift

Benign

0.095

Sift4G

Benign

0.062

Vest4

0.088

MVP

0.15

MPC

0.046

ClinPred

0.027

GERP RS

0.84

gMVP

0.19

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over