Variant 19-54240559-C-T 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_024318.5(LILRA6):c.973G>A(p.Val325Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 148,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 39)

Exomes 𝑓: 0.0029 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

LILRA6
NM_024318.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0970

Variant links:

Genes affected

LILRA6 (HGNC:15495): (leukocyte immunoglobulin like receptor A6) Predicted to enable inhibitory MHC class I receptor activity. Predicted to be involved in cytokine-mediated signaling pathway. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LILRA6 links:

LILRA6 (HGNC:):

LILRA6 links:

RPS9 (HGNC:10442): (ribosomal protein S9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS9 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=0.036391914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA6	NM_024318.5 linkuse as main transcript	c.973G>A	p.Val325Ile	missense_variant	6/8		NP_077294.3	U5XH19
LILRA6	NR_104098.2 linkuse as main transcript	n.926G>A		non_coding_transcript_exon_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA6	ENST00000396365.6 linkuse as main transcript	c.973G>A	p.Val325Ile	missense_variant	6/8	1		ENSP00000379651.2		Q6PI73

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

287

AN:

148406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000467

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00200

Gnomad ASJ

AF:

0.000937

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000951

Gnomad FIN

AF:

0.00261

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00302

Gnomad OTH

AF:

0.000991

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00295

AC:

4024

AN:

1365628

Hom.:

Cov.:

139

AF XY:

0.00286

AC XY:

1915

AN XY:

670464

show subpopulations

Gnomad4 AFR exome

AF:

0.000537

Gnomad4 AMR exome

AF:

0.00185

Gnomad4 ASJ exome

AF:

0.00255

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.00382

Gnomad4 NFE exome

AF:

0.00326

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00193

AC:

287

AN:

148528

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

127

AN XY:

72386

show subpopulations

Gnomad4 AFR

AF:

0.000466

Gnomad4 AMR

AF:

0.00199

Gnomad4 ASJ

AF:

0.000937

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000951

Gnomad4 FIN

AF:

0.00261

Gnomad4 NFE

AF:

0.00302

Gnomad4 OTH

AF:

0.000980

Alfa

AF:

0.000685

Hom.:

ESP6500AA

AF:

0.000240

AC:

ESP6500EA

AF:

0.000471

AC:

ExAC

AF:

0.000434

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

Sep 30, 2021

The c.973G>A (p.V325I) alteration is located in exon 6 (coding exon 6) of the LILRA6 gene. This alteration results from a G to A substitution at nucleotide position 973, causing the valine (V) at amino acid position 325 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

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.69

DANN

Benign

0.85

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.84

PROVEAN

Benign

-0.86

N;N

REVEL

Benign

0.037

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.031

D;D

Vest4

0.096

MVP

0.076

MPC

0.89

ClinPred

0.012

GERP RS

-0.17

gMVP

0.16

Splicing

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