rs4792311

chr17-13011692-G-Achr17-13011692-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018127.7(ELAC2):c.650C>T(p.Ser217Leu) variant causes a missense change. The variant allele was found at a frequency of 0.289 in 1,613,650 control chromosomes in the GnomAD database, including 69,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S217S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (5876 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63870 hom.)
• Consequence: ELAC2 NM_018127.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:7
• Conservation: PhyloP100: 3.72

Genes affected

ELAC2 (HGNC:14198): (elaC ribonuclease Z 2) The protein encoded by this gene has a C-terminal domain with tRNA 3′ processing endoribonuclease activity, which catalyzes the removal of the 3' trailer from precursor tRNAs. The protein also interacts with activated Smad family member 2 (Smad2) and its nuclear partner forkhead box H1 (also known as FAST-1), and reduced expression can suppress transforming growth factor-beta induced growth arrest. Mutations in this gene result in an increased risk of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-13011692-G-A is Benign according to our data. Variant chr17-13011692-G-A is described in ClinVar as [Benign]. Clinvar id is 5055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7	c.650C>T	p.Ser217Leu	missense_variant	7/24	ENST00000338034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9	c.650C>T	p.Ser217Leu	missense_variant	7/24	1	NM_018127.7	P2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41571 AN: 151738 Hom.: 5873 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.285

GnomAD3 exomes AF: 0.274 AC: 68792 AN: 251474 Hom.: 10210 AF XY: 0.277 AC XY: 37608 AN XY: 135908

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.0348

Gnomad SAS exome AF: 0.277

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.291 AC: 424894 AN: 1461794 Hom.: 63870 Cov.: 46 AF XY: 0.291 AC XY: 211680 AN XY: 727202

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.0318

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.274 AC: 41587 AN: 151856 Hom.: 5876 Cov.: 32 AF XY: 0.272 AC XY: 20195 AN XY: 74190

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.281

Alfa AF: 0.287 Hom.: 16838

Bravo AF: 0.267

TwinsUK AF: 0.299 AC: 1110

ALSPAC AF: 0.301 AC: 1161

ESP6500AA AF: 0.235 AC: 1034

ESP6500EA AF: 0.297 AC: 2552

ExAC AF: 0.271 AC: 32907

Asia WGS AF: 0.141 AC: 493 AN: 3478

EpiCase AF: 0.302

EpiControl AF: 0.298

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined oxidative phosphorylation defect type 17 Benign:4

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Genetics, Royal Melbourne Hospital	Oct 04, 2021	Population allele frequency is 27% (rs4792311; 75,983/277,124 alleles in gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Prostate cancer, hereditary, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2002

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 18, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Feb 15, 2016

- -

Prostate cancer, hereditary, 2;C3809526:Combined oxidative phosphorylation defect type 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.20
Cadd	Benign	21
Dann	Benign	0.58
DEOGEN2	Benign	0.018	T;.;T;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.66	T;T;T;T;T
MetaRNN	Benign	0.0041	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	-0.67	N;N;.;.;.
REVEL	Benign	0.15
Sift	Benign	0.32	T;T;.;.;.
Sift4G	Benign	0.39	T;T;.;.;.
Polyphen		0.36	B;P;.;.;.
Vest4		0.10
MPC		0.22
ClinPred		0.013	T
GERP RS		3.2
Varity_R		0.027
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -29

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

Publications

LitVar

Other links and lift over

dbSNP: rs4792311; hg19: chr17-12915009; COSMIC: COSV62031776; COSMIC: COSV62031776;