Variant 19-54595726-T-C 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.749T>C(p.Val250Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LILRA1
NM_006863.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.23

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04916507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA1	NM_006863.4 linkuse as main transcript	c.749T>C	p.Val250Ala	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.749T>C	p.Val250Ala	missense_variant	6/10	1	NM_006863.4	ENSP00000251372	P1	O75019-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

160

AN:

121040

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00231

Gnomad AMI

AF:

0.00137

Gnomad AMR

AF:

0.00158

Gnomad ASJ

AF:

0.000365

Gnomad EAS

AF:

0.000419

Gnomad SAS

AF:

0.000818

Gnomad FIN

AF:

0.00211

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000774

Gnomad OTH

AF:

0.000605

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251430

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000511

AC:

613

AN:

1198544

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

336

AN XY:

599802

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00239

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00175

Gnomad4 FIN exome

AF:

0.000396

Gnomad4 NFE exome

AF:

0.000348

Gnomad4 OTH exome

AF:

0.000432

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00132

AC:

160

AN:

121106

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

AN XY:

58984

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000365

Gnomad4 EAS

AF:

0.000421

Gnomad4 SAS

AF:

0.000819

Gnomad4 FIN

AF:

0.00211

Gnomad4 NFE

AF:

0.000774

Gnomad4 OTH

AF:

0.000600

Alfa

AF:

0.00430

Hom.:

ExAC

AF:

0.0000165

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

Mar 03, 2022

The c.749T>C (p.V250A) alteration is located in exon 6 (coding exon 5) of the LILRA1 gene. This alteration results from a T to C substitution at nucleotide position 749, causing the valine (V) at amino acid position 250 to be replaced by an alanine (A). 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

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.10

DANN

Benign

0.26

DEOGEN2

Benign

0.018

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00068

M_CAP

Benign

0.0012

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.019

Sift

Benign

0.31

Sift4G

Benign

0.36

Polyphen

0.050

Vest4

0.10

MutPred

0.38

Gain of catalytic residue at V250 (P = 0.1454);

MVP

0.061

MPC

0.034

ClinPred

0.65

GERP RS

-3.2

Varity_R

0.048

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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