chr4-56920284-G-T

Position:

• chr4-56920284-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005612.5(REST):​c.982+414G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 151,268 control chromosomes in the GnomAD database, including 63,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (63440 hom., cov: 27)
• Consequence: REST NM_005612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REST	NM_005612.5	c.982+414G>T		intron_variant		ENST00000309042.12	NP_005603.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REST	ENST00000309042.12	c.982+414G>T		intron_variant		1	NM_005612.5	ENSP00000311816	P1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138180 AN: 151150 Hom.: 63382 Cov.: 27

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.907

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.914 AC: 138296 AN: 151268 Hom.: 63440 Cov.: 27 AF XY: 0.911 AC XY: 67265 AN XY: 73842

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.913

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.904

Alfa AF: 0.904 Hom.: 133840

Bravo AF: 0.917

Asia WGS AF: 0.738 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.4
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1713985; hg19: chr4-57786450;