rs12512164
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_025074.7(FRAS1):c.3406G>A(p.Glu1136Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,613,212 control chromosomes in the GnomAD database, including 57,385 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_025074.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.3406G>A | p.Glu1136Lys | missense_variant | 27/74 | ENST00000512123.4 | |
FRAS1 | NM_001166133.2 | c.3406G>A | p.Glu1136Lys | missense_variant | 27/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.3406G>A | p.Glu1136Lys | missense_variant | 27/74 | 5 | NM_025074.7 | P1 | |
FRAS1 | ENST00000325942.11 | c.3406G>A | p.Glu1136Lys | missense_variant | 27/42 | 1 | |||
FRAS1 | ENST00000682513.1 | c.3406G>A | p.Glu1136Lys | missense_variant | 27/64 | ||||
FRAS1 | ENST00000684159.1 | c.3406G>A | p.Glu1136Lys | missense_variant | 27/45 |
Frequencies
GnomAD3 genomes ? AF: 0.242 AC: 36694AN: 151878Hom.: 4816 Cov.: 32
GnomAD3 exomes AF: 0.269 AC: 66797AN: 248708Hom.: 9596 AF XY: 0.263 AC XY: 35506AN XY: 134920
GnomAD4 exome AF: 0.265 AC: 386883AN: 1461216Hom.: 52564 Cov.: 34 AF XY: 0.263 AC XY: 191152AN XY: 726904
GnomAD4 genome ? AF: 0.242 AC: 36720AN: 151996Hom.: 4821 Cov.: 32 AF XY: 0.242 AC XY: 17995AN XY: 74284
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 18, 2014 | - - |
Fraser syndrome 1 Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at