rs61734495

Variant names:

• chr19-54241620-C-T
• rs61734495
• NM_024318.5:c.614G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024318.5(LILRA6):​c.614G>A​(p.Arg205Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,255,248 control chromosomes in the GnomAD database, including 46,194 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (4176 hom., cov: 23)
  • Exomes 𝑓: 0.29 (42018 hom.)
• Consequence: LILRA6 NM_024318.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.628
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002255261).
• BP6: Variant 19-54241620-C-T is Benign according to our data. Variant chr19-54241620-C-T is described in ClinVar as Benign. ClinVar VariationId is 403040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024318.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRA6	NM_024318.5	MANE Select	c.614G>A	p.Arg205Gln	missense	Exon 4 of 8	NP_077294.3	U5XH19
	LILRA6	NR_104098.2		n.611+42G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRA6	ENST00000396365.7	TSL:1 MANE Select	c.614G>A	p.Arg205Gln	missense	Exon 4 of 8	ENSP00000379651.2	Q6PI73
	LILRA6	ENST00000430421.5	TSL:1	n.572+42G>A		intron	N/A	ENSP00000412929.1	Q6PI73
	LILRA6	ENST00000245621.6	TSL:5	c.614G>A	p.Arg205Gln	missense	Exon 4 of 7	ENSP00000245621.4	B5ME96

Frequencies

GnomAD3 genomes AF: 0.305 AC: 35130 AN: 115262 Hom.: 4175 Cov.: 23

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.310

GnomAD2 exomes AF: 0.0533 AC: 10421 AN: 195684 AF XY: 0.0508

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.107

Gnomad FIN exome AF: 0.0607

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0564

GnomAD4 exome AF: 0.290 AC: 330699 AN: 1139888 Hom.: 42018 Cov.: 38 AF XY: 0.295 AC XY: 168075 AN XY: 569790

African (AFR) AF: 0.315 AC: 8255 AN: 26168

American (AMR) AF: 0.285 AC: 11106 AN: 39030

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 5090 AN: 20688

East Asian (EAS) AF: 0.363 AC: 12796 AN: 35272

South Asian (SAS) AF: 0.387 AC: 25653 AN: 66220

European-Finnish (FIN) AF: 0.346 AC: 16209 AN: 46880

Middle Eastern (MID) AF: 0.313 AC: 1337 AN: 4278

European-Non Finnish (NFE) AF: 0.276 AC: 235569 AN: 853392

Other (OTH) AF: 0.306 AC: 14684 AN: 47960

GnomAD4 genome AF: 0.305 AC: 35172 AN: 115360 Hom.: 4176 Cov.: 23 AF XY: 0.304 AC XY: 16927 AN XY: 55636

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

African (AFR) AF: 0.326 AC: 10428 AN: 32010

American (AMR) AF: 0.317 AC: 3683 AN: 11636

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 542 AN: 2502

East Asian (EAS) AF: 0.355 AC: 1493 AN: 4204

South Asian (SAS) AF: 0.360 AC: 1062 AN: 2948

European-Finnish (FIN) AF: 0.276 AC: 2118 AN: 7664

Middle Eastern (MID) AF: 0.242 AC: 47 AN: 194

European-Non Finnish (NFE) AF: 0.291 AC: 15108 AN: 51920

Other (OTH) AF: 0.313 AC: 487 AN: 1558

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.202 Hom.: 577

ExAC AF: 0.0352 AC: 4094

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.71
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00019	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.63
PROVEAN	Benign	1.4	N
REVEL	Benign	0.020
Sift	Benign	0.85	T
Sift4G	Benign	0.60	T
Vest4		0.029
MPC		1.1
ClinPred		0.000020	T
GERP RS		2.4
gMVP		0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs61734495; hg19: chr19-54745496; COSMIC: COSV54432752; COSMIC: COSV54432752;