rs3796530
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_005612.5(REST):c.2229G>A(p.Glu743=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,383,968 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 10 hom. )
Consequence
REST
NM_005612.5 synonymous
NM_005612.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.525
Genes affected
REST (HGNC:9966): (RE1 silencing transcription factor) This gene was initially identified as a transcriptional repressor that represses neuronal genes in non-neuronal tissues. However, depending on the cellular context, this gene can act as either an oncogene or a tumor suppressor. The encoded protein is a member of the Kruppel-type zinc finger transcription factor family. It represses transcription by binding a DNA sequence element called the neuron-restrictive silencer element. The protein is also found in undifferentiated neuronal progenitor cells and it is thought that this repressor may act as a master negative regulator of neurogenesis. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 4-56931087-G-A is Benign according to our data. Variant chr4-56931087-G-A is described in ClinVar as [Benign]. Clinvar id is 789137.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.525 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000996 (130/130570) while in subpopulation EAS AF= 0.0207 (94/4544). AF 95% confidence interval is 0.0173. There are 1 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 130 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REST | NM_005612.5 | c.2229G>A | p.Glu743= | synonymous_variant | 4/4 | ENST00000309042.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REST | ENST00000309042.12 | c.2229G>A | p.Glu743= | synonymous_variant | 4/4 | 1 | NM_005612.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000996 AC: 130AN: 130492Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000847 AC: 210AN: 247856Hom.: 2 AF XY: 0.000888 AC XY: 119AN XY: 134038
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GnomAD4 exome AF: 0.000530 AC: 664AN: 1253398Hom.: 10 Cov.: 32 AF XY: 0.000563 AC XY: 353AN XY: 626608
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GnomAD4 genome ? AF: 0.000996 AC: 130AN: 130570Hom.: 1 Cov.: 32 AF XY: 0.00111 AC XY: 71AN XY: 63916
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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