rs10492963

Positions:

• chr1-8750282-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.-145+66878G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 524,422 control chromosomes in the GnomAD database, including 14,175 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 0.20 (3517 hom., cov: 31)
  • Exomes 𝑓: 0.23 (10658 hom.)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERE	NM_001042681.2	c.-145+66878G>A		intron_variant		ENST00000400908.7
RERE	NM_012102.4	c.-145+42122G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.-145+66878G>A		intron_variant		1	NM_001042681.2	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30521 AN: 151808 Hom.: 3517 Cov.: 31

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.231 AC: 86166 AN: 372498 Hom.: 10658 AF XY: 0.232 AC XY: 45842 AN XY: 197996

Gnomad4 AFR exome AF: 0.0927

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.201 AC: 30524 AN: 151924 Hom.: 3517 Cov.: 31 AF XY: 0.200 AC XY: 14869 AN XY: 74234

Gnomad4 AFR AF: 0.0916

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.263

Alfa AF: 0.241 Hom.: 2378

Bravo AF: 0.201

Asia WGS AF: 0.202 AC: 701 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	1.1
DANN	Benign	0.74

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: rs10492963; hg19: chr1-8810341;