Variant 19-54595699-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006863.4(LILRA1):c.722G>A(p.Ser241Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.0046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LILRA1
NM_006863.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.50

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:

LILRA1 (HGNC:):

LILRA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022366285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA1	NM_006863.4 linkuse as main transcript	c.722G>A	p.Ser241Asn	missense_variant	6/10	ENST00000251372.8	NP_006854.1	O75019-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA1	ENST00000251372.8 linkuse as main transcript	c.722G>A	p.Ser241Asn	missense_variant	6/10	1	NM_006863.4	ENSP00000251372.3		O75019-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

487

AN:

106470

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00679

Gnomad AMI

AF:

0.00647

Gnomad AMR

AF:

0.00549

Gnomad ASJ

AF:

0.00434

Gnomad EAS

AF:

0.000657

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00566

Gnomad MID

AF:

0.00505

Gnomad NFE

AF:

0.00324

Gnomad OTH

AF:

0.00407

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251328

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00259

AC:

3121

AN:

1207308

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

1711

AN XY:

602484

show subpopulations

Gnomad4 AFR exome

AF:

0.00848

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.000103

Gnomad4 SAS exome

AF:

0.00880

Gnomad4 FIN exome

AF:

0.00187

Gnomad4 NFE exome

AF:

0.00144

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00461

AC:

491

AN:

106496

Hom.:

Cov.:

AF XY:

0.00548

AC XY:

285

AN XY:

51986

show subpopulations

Gnomad4 AFR

AF:

0.00689

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.00434

Gnomad4 EAS

AF:

0.000659

Gnomad4 SAS

AF:

0.00603

Gnomad4 FIN

AF:

0.00566

Gnomad4 NFE

AF:

0.00326

Gnomad4 OTH

AF:

0.00403

Alfa

AF:

0.00373

Hom.:

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

Jul 02, 2024

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

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0010

DANN

Benign

0.51

DEOGEN2

Benign

0.0010

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.00055

M_CAP

Benign

0.00093

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.68

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.47

REVEL

Benign

0.0080

Sift

Benign

0.82

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.076

MutPred

0.30

Loss of sheet (P = 0.0817);

MVP

0.072

MPC

0.023

ClinPred

0.043

GERP RS

-3.2

Varity_R

0.028

gMVP

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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