rs4908760

Positions:

• chr1-8466082-G-A
• chr1-8466082-G-C
• chr1-8466082-G-T

Variant summary

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

The NM_001042681.2(RERE):​c.1105-59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,389,238 control chromosomes in the GnomAD database, including 286,425 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 0.67 (35486 hom., cov: 30)
  • Exomes 𝑓: 0.63 (250939 hom.)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERE	NM_001042681.2	c.1105-59C>T		intron_variant		ENST00000400908.7
RERE	NM_012102.4	c.1105-59C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.1105-59C>T		intron_variant		1	NM_001042681.2	P1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102342 AN: 151852 Hom.: 35438 Cov.: 30

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.632 AC: 782108 AN: 1237268 Hom.: 250939 AF XY: 0.627 AC XY: 384712 AN XY: 613598

Gnomad4 AFR exome AF: 0.812

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.674 AC: 102451 AN: 151970 Hom.: 35486 Cov.: 30 AF XY: 0.677 AC XY: 50274 AN XY: 74266

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.599

Alfa AF: 0.607 Hom.: 61775

Bravo AF: 0.675

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.38

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: rs4908760; hg19: chr1-8526142;