4-56930734-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005612.5(REST):c.1876G>A(p.Val626Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,601,638 control chromosomes in the GnomAD database, including 4,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V626L) has been classified as Uncertain significance.
Frequency
Consequence
NM_005612.5 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REST | NM_005612.5 | c.1876G>A | p.Val626Ile | missense_variant | 4/4 | ENST00000309042.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REST | ENST00000309042.12 | c.1876G>A | p.Val626Ile | missense_variant | 4/4 | 1 | NM_005612.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0866 AC: 13167AN: 152068Hom.: 870 Cov.: 33
GnomAD3 exomes AF: 0.0887 AC: 20960AN: 236230Hom.: 1945 AF XY: 0.0768 AC XY: 9852AN XY: 128344
GnomAD4 exome AF: 0.0512 AC: 74225AN: 1449452Hom.: 3834 Cov.: 33 AF XY: 0.0488 AC XY: 35150AN XY: 720890
GnomAD4 genome AF: 0.0866 AC: 13177AN: 152186Hom.: 877 Cov.: 33 AF XY: 0.0889 AC XY: 6617AN XY: 74406
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2019 | This variant is associated with the following publications: (PMID: 22530801) - |
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