Variant rs3796530 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005612.5(REST):c.2229G>A(p.Glu743Glu) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.525

Variant links:

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]

REST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
REST	NM_005612.5 link	c.2229G>A	p.Glu743Glu	synonymous_variant	4/4	ENST00000309042.12	NP_005603.3	Q13127-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REST	ENST00000309042.12 link	c.2229G>A	p.Glu743Glu	synonymous_variant	4/4	1	NM_005612.5	ENSP00000311816.7		Q13127-1

Frequencies

GnomAD3 genomes

AF:

0.000996

AC:

130

AN:

130492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000349

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000296

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0206

Gnomad SAS

AF:

0.00152

Gnomad FIN

AF:

0.000338

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000154

Gnomad OTH

AF:

0.000539

GnomAD3 exomes

AF:

0.000847

AC:

210

AN:

247856

Hom.:

AF XY:

0.000888

AC XY:

119

AN XY:

134038

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0108

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000530

AC:

664

AN:

1253398

Hom.:

Cov.:

AF XY:

0.000563

AC XY:

353

AN XY:

626608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.000519

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000573

Gnomad4 OTH exome

AF:

0.000402

GnomAD4 genome

AF:

0.000996

AC:

130

AN:

130570

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

63916

show subpopulations

Gnomad4 AFR

AF:

0.000348

Gnomad4 AMR

AF:

0.000295

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0207

Gnomad4 SAS

AF:

0.00152

Gnomad4 FIN

AF:

0.000338

Gnomad4 NFE

AF:

0.000154

Gnomad4 OTH

AF:

0.000539

Alfa

AF:

0.0589

Hom.:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.36

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over