rs77484245
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004453.4(ETFDH):āc.1533T>Cā(p.Asp511=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,614,166 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0053 ( 7 hom., cov: 32)
Exomes š: 0.0061 ( 58 hom. )
Consequence
ETFDH
NM_004453.4 synonymous
NM_004453.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.134
Genes affected
ETFDH (HGNC:3483): (electron transfer flavoprotein dehydrogenase) This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. Mutations in this gene are associated with glutaric acidemia. Alternatively spliced transcript variants that encode distinct isoforms have been observed. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 4-158706693-T-C is Benign according to our data. Variant chr4-158706693-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 137235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.134 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00532 (811/152330) while in subpopulation NFE AF= 0.00541 (368/68030). AF 95% confidence interval is 0.00495. There are 7 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETFDH | NM_004453.4 | c.1533T>C | p.Asp511= | synonymous_variant | 12/13 | ENST00000511912.6 | |
ETFDH | NM_001281737.2 | c.1392T>C | p.Asp464= | synonymous_variant | 11/12 | ||
ETFDH | NM_001281738.1 | c.1350T>C | p.Asp450= | synonymous_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETFDH | ENST00000511912.6 | c.1533T>C | p.Asp511= | synonymous_variant | 12/13 | 1 | NM_004453.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00533 AC: 811AN: 152212Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.00657 AC: 1653AN: 251440Hom.: 21 AF XY: 0.00673 AC XY: 914AN XY: 135888
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GnomAD4 exome AF: 0.00608 AC: 8894AN: 1461836Hom.: 58 Cov.: 31 AF XY: 0.00592 AC XY: 4307AN XY: 727224
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GnomAD4 genome AF: 0.00532 AC: 811AN: 152330Hom.: 7 Cov.: 32 AF XY: 0.00646 AC XY: 481AN XY: 74502
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Multiple acyl-CoA dehydrogenase deficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 29, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 12, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | ETFDH: BP4, BP7, BS2 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 17, 2013 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at