rs2120461

chr1-8387662-C-T

Variant summary

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

The NM_001042681.2(RERE):c.1285-21688G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,000 control chromosomes in the GnomAD database, including 35,951 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 0.68 (35951 hom., cov: 32)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

Genes affected

RERE (HGNC:9965): (arginine-glutamic acid dipeptide repeats) This gene encodes a member of the atrophin family of arginine-glutamic acid (RE) dipeptide repeat-containing proteins. The encoded protein co-localizes with a transcription factor in the nucleus, and its overexpression triggers apoptosis. A similar protein in mouse associates with histone deacetylase and is thought to function as a transcriptional co-repressor during embryonic development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERE	NM_001042681.2	c.1285-21688G>A		intron_variant		ENST00000400908.7
RERE	NM_001042682.2	c.-378-21688G>A		intron_variant
RERE	NM_012102.4	c.1285-21688G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.1285-21688G>A		intron_variant		1	NM_001042681.2	P1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103873 AN: 151882 Hom.: 35916 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.684 AC: 103962 AN: 152000 Hom.: 35951 Cov.: 32 AF XY: 0.685 AC XY: 50886 AN XY: 74304

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.726

Alfa AF: 0.675 Hom.: 4465

Bravo AF: 0.693

Asia WGS AF: 0.787 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.0
Dann	Benign	0.58
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

Other links and lift over

dbSNP: rs2120461; hg19: chr1-8447722; COSMIC: COSV61939080;