rs4792311
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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
ENST00000338034.9 missense
Scores
1
16
Clinical Significance
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]
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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 | 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 | c.650C>T | p.Ser217Leu | missense_variant | 7/24 | 1 | NM_018127.7 | ENSP00000337445 | P2 |
Frequencies
GnomAD3 genomes AF: 0.274 AC: 41571AN: 151738Hom.: 5873 Cov.: 32
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GnomAD3 exomes AF: 0.274 AC: 68792AN: 251474Hom.: 10210 AF XY: 0.277 AC XY: 37608AN XY: 135908
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GnomAD4 exome AF: 0.291 AC: 424894AN: 1461794Hom.: 63870 Cov.: 46 AF XY: 0.291 AC XY: 211680AN XY: 727202
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GnomAD4 genome AF: 0.274 AC: 41587AN: 151856Hom.: 5876 Cov.: 32 AF XY: 0.272 AC XY: 20195AN XY: 74190
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
P;P;P
PROVEAN
Benign
N;N;.;.;.
REVEL
Benign
Sift
Benign
T;T;.;.;.
Sift4G
Benign
T;T;.;.;.
Polyphen
B;P;.;.;.
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -29
Find out detailed SpliceAI scores and Pangolin per-transcript scores at