rs1799958
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000017.4(ACADS):c.625G>A(p.Gly209Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,613,942 control chromosomes in the GnomAD database, including 54,922 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000017.4 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACADS | NM_000017.4 | c.625G>A | p.Gly209Ser | missense_variant, splice_region_variant | Exon 6 of 10 | ENST00000242592.9 | NP_000008.1 | |
ACADS | NM_001302554.2 | c.613G>A | p.Gly205Ser | missense_variant, splice_region_variant | Exon 6 of 10 | NP_001289483.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACADS | ENST00000242592.9 | c.625G>A | p.Gly209Ser | missense_variant, splice_region_variant | Exon 6 of 10 | 1 | NM_000017.4 | ENSP00000242592.4 | ||
ACADS | ENST00000411593.2 | c.613G>A | p.Gly205Ser | missense_variant, splice_region_variant | Exon 6 of 10 | 2 | ENSP00000401045.2 |
Frequencies
GnomAD3 genomes AF: 0.211 AC: 32093AN: 152008Hom.: 4233 Cov.: 33
GnomAD3 exomes AF: 0.265 AC: 66490AN: 251146Hom.: 9719 AF XY: 0.267 AC XY: 36213AN XY: 135784
GnomAD4 exome AF: 0.258 AC: 377749AN: 1461816Hom.: 50683 Cov.: 74 AF XY: 0.261 AC XY: 189472AN XY: 727218
GnomAD4 genome AF: 0.211 AC: 32101AN: 152126Hom.: 4239 Cov.: 33 AF XY: 0.218 AC XY: 16232AN XY: 74346
ClinVar
Submissions by phenotype
Deficiency of butyryl-CoA dehydrogenase Pathogenic:1Benign:4Other:2
- -
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
- -
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
- -
- -
- -
not provided Benign:4Other:1
- -
- -
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. -
Variant interpreted as Benign and reported on 08-28-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -
- -
not specified Benign:3
- -
- -
- -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at