Variant chr19-54278296-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/18 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 2364161.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRB2	NM_001080978.4 linkuse as main transcript	c.1222T>A	p.Ser408Thr	missense_variant	7/14	ENST00000314446.10	NP_001074447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRB2	ENST00000314446.10 linkuse as main transcript	c.1222T>A	p.Ser408Thr	missense_variant	7/14	1	NM_001080978.4	ENSP00000319960	A2	Q8N423-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

137274

Hom.:

Cov.:

FAILED QC

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

GnomAD3 exomes

AF:

0.000286

AC:

AN:

251442

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

135892

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 SAS exome

AF:

0.000621

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

Gnomad4 AFR exome

AF:

0.000340

Gnomad4 AMR exome

AF:

0.000522

Gnomad4 ASJ exome

AF:

0.0000779

Gnomad4 EAS exome

AF:

0.00714

Gnomad4 SAS exome

AF:

0.000754

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.000435

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

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000364

Gnomad4 ASJ

AF:

0.000318

Gnomad4 EAS

AF:

0.00223

Gnomad4 SAS

AF:

0.00120

Gnomad4 FIN

AF:

0.000522

Gnomad4 NFE

AF:

0.000239

Gnomad4 OTH

AF:

0.00206

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.4

DANN

Benign

0.63

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.68

.;.;T;.;.

M_CAP

Benign

0.0029

MetaRNN

Benign

0.028

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.0

N;N;N;N;N

REVEL

Benign

0.051

Sift

Benign

0.095

T;T;T;T;T

Sift4G

Benign

0.062

T;T;T;T;T

Vest4

0.088

MVP

0.15

MPC

0.046

ClinPred

0.027

GERP RS

0.84

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over