chr19-54241032-C-T

Position:

• chr19-54241032-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000396365.7(LILRA6):​c.754G>A​(p.Asp252Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRA6 ENST00000396365.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18975079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LILRA6	NM_024318.5	c.754G>A	p.Asp252Asn	missense_variant	5/8	ENST00000396365.7
LILRA6	NR_104098.2	n.707G>A		non_coding_transcript_exon_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LILRA6	ENST00000396365.7	c.754G>A	p.Asp252Asn	missense_variant	5/8	1	NM_024318.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3037 AN: 146460 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00824

Gnomad AMI AF: 0.0112

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0262

GnomAD3 exomes AF: 0.0000398 AC: 10 AN: 251386 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135878

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000579

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0318 AC: 45064 AN: 1417394 Hom.: 0 Cov.: 81 AF XY: 0.0323 AC XY: 22791 AN XY: 704564

Gnomad4 AFR exome AF: 0.00922

Gnomad4 AMR exome AF: 0.0549

Gnomad4 ASJ exome AF: 0.0306

Gnomad4 EAS exome AF: 0.0260

Gnomad4 SAS exome AF: 0.0532

Gnomad4 FIN exome AF: 0.0174

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0337

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0208 AC: 3044 AN: 146580 Hom.: 0 Cov.: 32 AF XY: 0.0210 AC XY: 1503 AN XY: 71582

Gnomad4 AFR AF: 0.00834

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.0260

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0259

ExAC AF: 0.0000412 AC: 5

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

Jul 06, 2021

The c.754G>A (p.D252N) alteration is located in exon 5 (coding exon 5) of the LILRA6 gene. This alteration results from a G to A substitution at nucleotide position 754, causing the aspartic acid (D) at amino acid position 252 to be replaced by an asparagine (N). 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	-0.53	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.13	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.059
Sift	Benign	0.070	T;T
Sift4G	Benign	0.073	T;T
Vest4		0.36
MutPred		0.58		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.24
MPC		1.5
ClinPred		0.31	T
GERP RS		1.3
gMVP		0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs750604302; hg19: chr19-54744908;