chr19-54241620-C-T

Position:

• chr19-54241620-C-T

Variant summary

Our verdict is Benign. Variant got -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. 10/15 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

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 (HGNC:):

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 Benign. Variant got -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 id is 403040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA6	NM_024318.5	c.614G>A	p.Arg205Gln	missense_variant	4/8		NP_077294.3
LILRA6	NR_104098.2	n.611+42G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA6	ENST00000396365.6	c.614G>A	p.Arg205Gln	missense_variant	4/8	1		ENSP00000379651.2

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

GnomAD3 exomes AF: 0.0533 AC: 10421 AN: 195684 Hom.: 396 AF XY: 0.0508 AC XY: 5412 AN XY: 106624

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 SAS exome AF: 0.0539

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

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.306

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

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.313

Alfa AF: 0.202 Hom.: 577

ExAC AF: 0.0352 AC: 4094

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.020
Sift	Benign	0.85	T;T
Sift4G	Benign	0.60	T;T
Vest4		0.029
MPC		1.1
ClinPred		0.000020	T
GERP RS		2.4
gMVP		0.095

Splicing

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

Publications

LitVar

Other links and lift over

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