rs4792311

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000338034.9(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
ENST00000338034.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:8

Conservation

PhyloP100: 3.72

Variant links:

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]

ELAC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
ELAC2	NM_018127.7 linkuse as main transcript	c.650C>T	p.Ser217Leu	missense_variant	7/24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9 linkuse as main transcript	c.650C>T	p.Ser217Leu	missense_variant	7/24	1	NM_018127.7	ENSP00000337445	P2	Q9BQ52-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41571

AN:

151738

Hom.:

5873

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.291

AC XY:

211680

AN XY:

727202

show subpopulations

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.:

AF XY:

0.272

AC XY:

20195

AN XY:

74190

show subpopulations

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:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation defect type 17

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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 -

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 15, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

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

BayesDel_noAF

Benign

-0.20

CADD

Benign

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

LIST_S2

Benign

0.66

T;T;T;T;T

MetaRNN

Benign

0.0041

T;T;T;T;T

MetaSVM

Benign

-1.0

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over