rs374661645
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_018100.4(EFHC1):c.151C>T(p.Arg51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_018100.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.151C>T | p.Arg51Trp | missense_variant | 2/11 | ENST00000371068.11 | NP_060570.2 | |
EFHC1 | NM_001172420.2 | c.94C>T | p.Arg32Trp | missense_variant | 3/12 | NP_001165891.1 | ||
EFHC1 | NR_033327.2 | n.220C>T | non_coding_transcript_exon_variant | 2/10 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251440Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135892
GnomAD4 exome AF: 0.0000971 AC: 142AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000784 AC XY: 57AN XY: 727246
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74272
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2014 | The R51W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R51W variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The variant is found in EPILEPSY panel(s). - |
Absence seizure;C0270853:Juvenile myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at