19-54240559-C-T

Position:

• chr19-54240559-C-T

Variant summary

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

The ENST00000396365.7(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 ENST00000396365.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0970

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]

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]

ACMG classification

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	UniProt
LILRA6	NM_024318.5	c.973G>A	p.Val325Ile	missense_variant	6/8	ENST00000396365.7
LILRA6	NR_104098.2	n.926G>A		non_coding_transcript_exon_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LILRA6	ENST00000396365.7	c.973G>A	p.Val325Ile	missense_variant	6/8	1	NM_024318.5	P1
LILRA6	ENST00000430421.5	c.*305G>A		3_prime_UTR_variant, NMD_transcript_variant	6/10	1
LILRA6	ENST00000245621.6	c.973G>A	p.Val325Ile	missense_variant	6/7	5
RPS9	ENST00000448962.5	c.*183-6533C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 287 AN: 148406 Hom.: 0 Cov.: 39

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.: 1 Cov.: 139 AF XY: 0.00286 AC XY: 1915 AN XY: 670464

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.: 0 Cov.: 39 AF XY: 0.00175 AC XY: 127 AN XY: 72386

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.: 0

ESP6500AA AF: 0.000240 AC: 1

ESP6500EA AF: 0.000471 AC: 4

ExAC AF: 0.000434 AC: 52

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.69
DANN	Benign	0.85
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-0.84	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
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	T
GERP RS		-0.17
gMVP		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199737866; hg19: chr19-54744435; COSMIC: COSV99557443; COSMIC: COSV99557443;