ENST00000396365.7:c.358G>T

Variant names:

• chr19-54241876-C-A
• rs1132591
• ENST00000396365.7:c.358G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000396365.7(LILRA6):​c.358G>T​(p.Ala120Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,292,156 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000025 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000010 (2 hom.)
• Consequence: LILRA6 ENST00000396365.7 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.12
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023920357).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LILRA6	NM_024318.5	c.358G>T	p.Ala120Ser	missense_variant, splice_region_variant	Exon 4 of 8		NP_077294.3
LILRA6	NR_104098.2	n.397G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LILRA6	ENST00000396365.7	c.358G>T	p.Ala120Ser	missense_variant, splice_region_variant	Exon 4 of 8	1		ENSP00000379651.2

Frequencies

GnomAD3 genomes AF: 0.0000253 AC: 3 AN: 118614 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000396

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000102 AC: 12 AN: 1173542 Hom.: 2 Cov.: 41 AF XY: 0.0000103 AC XY: 6 AN XY: 579976

African (AFR) AF: 0.00 AC: 0 AN: 31794

American (AMR) AF: 0.00 AC: 0 AN: 39824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19864

East Asian (EAS) AF: 0.000133 AC: 5 AN: 37550

South Asian (SAS) AF: 0.0000168 AC: 1 AN: 59584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.000251 AC: 1 AN: 3984

European-Non Finnish (NFE) AF: 0.00000561 AC: 5 AN: 891236

Other (OTH) AF: 0.00 AC: 0 AN: 49188

GnomAD4 genome AF: 0.0000253 AC: 3 AN: 118614 Hom.: 0 Cov.: 19 AF XY: 0.0000175 AC XY: 1 AN XY: 57178

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000273 AC: 1 AN: 36576

American (AMR) AF: 0.00 AC: 0 AN: 11634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2514

East Asian (EAS) AF: 0.00 AC: 0 AN: 4602

South Asian (SAS) AF: 0.00 AC: 0 AN: 2838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.0000396 AC: 2 AN: 50548

Other (OTH) AF: 0.00 AC: 0 AN: 1582

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000000565104), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.430 Hom.: 4473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
CADD	Benign	0.0010
DEOGEN2	Benign	0.017	.;T
LIST_S2	Benign	0.30	T;T
MetaRNN	Benign	0.024	T;T
PhyloP100		-6.1
Sift4G	Benign	0.44	T;T
Vest4		0.11
gMVP		0.14

Splicing

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

Other links and lift over

dbSNP: rs1132591; hg19: -;