rs2252865

Positions:

• chr1-8362616-T-C

Variant summary

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

The NM_001042681.2(RERE):​c.1902+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,596,282 control chromosomes in the GnomAD database, including 374,411 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 0.73 (40633 hom., cov: 32)
  • Exomes 𝑓: 0.68 (333778 hom.)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RERE	NM_001042681.2	c.1902+67A>G		intron_variant		ENST00000400908.7	NP_001036146.1
RERE	NM_001042682.2	c.240+67A>G		intron_variant			NP_001036147.1
RERE	NM_012102.4	c.1902+67A>G		intron_variant			NP_036234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.1902+67A>G		intron_variant		1	NM_001042681.2	ENSP00000383700	P1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110266 AN: 151974 Hom.: 40579 Cov.: 32

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.677 AC: 977359 AN: 1444190 Hom.: 333778 AF XY: 0.679 AC XY: 488102 AN XY: 719042

Gnomad4 AFR exome AF: 0.818

Gnomad4 AMR exome AF: 0.787

Gnomad4 ASJ exome AF: 0.807

Gnomad4 EAS exome AF: 0.893

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.726 AC: 110378 AN: 152092 Hom.: 40633 Cov.: 32 AF XY: 0.725 AC XY: 53910 AN XY: 74332

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.745

Alfa AF: 0.690 Hom.: 52390

Bravo AF: 0.742

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	-0.97
CADD	Benign	1.0
DANN	Benign	0.45
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: rs2252865; hg19: chr1-8422676;