Variant chr19-54595699-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000251372.8(LILRA1):c.722G>T(p.Ser241Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,457,002 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

LILRA1
ENST00000251372.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U: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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07372838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA1	NM_006863.4 linkuse as main transcript	c.722G>T	p.Ser241Ile	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>T	p.Ser241Ile	missense_variant	6/10	1	NM_006863.4	ENSP00000251372.3		O75019-1

Frequencies

GnomAD3 genomes

AF:

0.0000242

AC:

AN:

124220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000808

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000177

Gnomad OTH

AF:

0.000589

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251328

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1332782

Hom.:

Cov.:

AF XY:

0.0000255

AC XY:

AN XY:

665524

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000358

GnomAD4 genome

AF:

0.0000242

AC:

AN:

124220

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

60478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000808

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000177

Gnomad4 OTH

AF:

0.000589

Alfa

AF:

0.0000490

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

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

Apr 08, 2024

The c.722G>T (p.S241I) alteration is located in exon 6 (coding exon 5) of the LILRA1 gene. This alteration results from a G to T substitution at nucleotide position 722, causing the serine (S) at amino acid position 241 to be replaced by an isoleucine (I). 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0060

DANN

Benign

0.73

DEOGEN2

Benign

0.072

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0034

M_CAP

Benign

0.0012

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.053

Sift

Uncertain

0.013

Sift4G

Uncertain

0.043

Polyphen

0.014

Vest4

0.26

MutPred

0.42

Loss of disorder (P = 0.0345);

MVP

0.072

MPC

0.029

ClinPred

0.14

GERP RS

-3.2

Varity_R

0.11

gMVP

0.11

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