Variant 19-54595864-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006863.4(LILRA1):c.887G>C(p.Arg296Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.41 ( 0 hom., cov: 41)

Exomes 𝑓: 0.46 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

LILRA1
NM_006863.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.994

Variant links:

Genes affected

LILRA1 (HGNC:6602): (leukocyte immunoglobulin like receptor A1) This gene encodes an activating member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein is predominantly expressed in B cells, interacts with major histocompatibility complex class I ligands, and contributes to the regulation of immune responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

LILRA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20809928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA1	NM_006863.4 linkuse as main transcript	c.887G>C	p.Arg296Thr	missense_variant	6/10	ENST00000251372.8	NP_006854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA1	ENST00000251372.8 linkuse as main transcript	c.887G>C	p.Arg296Thr	missense_variant	6/10	1	NM_006863.4	ENSP00000251372	P1	O75019-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

45454

AN:

109738

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.0000558

AC:

AN:

250720

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.459

AC:

614945

AN:

1339504

Hom.:

Cov.:

200

AF XY:

0.460

AC XY:

305450

AN XY:

664382

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.458

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.472

Gnomad4 OTH exome

AF:

0.464

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.414

AC:

45486

AN:

109810

Hom.:

Cov.:

AF XY:

0.410

AC XY:

21978

AN XY:

53636

show subpopulations

Gnomad4 AFR

AF:

0.403

Gnomad4 AMR

AF:

0.407

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.442

Gnomad4 OTH

AF:

0.435

Alfa

AF:

0.000367

Hom.:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.887G>C (p.R296T) alteration is located in exon 6 (coding exon 5) of the LILRA1 gene. This alteration results from a G to C substitution at nucleotide position 887, causing the arginine (R) at amino acid position 296 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.046

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.029

M_CAP

Benign

0.0017

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.11

Sift

Benign

0.091

Sift4G

Benign

0.079

Polyphen

0.13

Vest4

0.30

MutPred

0.69

Gain of phosphorylation at R296 (P = 0.0681);

MVP

0.14

MPC

0.10

ClinPred

0.36

GERP RS

0.64

Varity_R

0.20

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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