1-8352875-C-T

Position:

• chr1-8352875-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.*2212G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,438 control chromosomes in the GnomAD database, including 16,886 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 0.46 (16846 hom., cov: 33)
  • Exomes 𝑓: 0.44 (40 hom.)
• Consequence: RERE NM_001042681.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERE	NM_001042681.2	c.*2212G>A		3_prime_UTR_variant	23/23	ENST00000400908.7
RERE	NM_001042682.2	c.*2212G>A		3_prime_UTR_variant	13/13
RERE	NM_012102.4	c.*2212G>A		3_prime_UTR_variant	24/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.*2212G>A		3_prime_UTR_variant	23/23	1	NM_001042681.2	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69369 AN: 151962 Hom.: 16832 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.444 AC: 159 AN: 358 Hom.: 40 Cov.: 0 AF XY: 0.398 AC XY: 82 AN XY: 206

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.456 AC: 69410 AN: 152080 Hom.: 16846 Cov.: 33 AF XY: 0.459 AC XY: 34099 AN XY: 74340

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.471

Alfa AF: 0.476 Hom.: 25752

Bravo AF: 0.464

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.025
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: rs8627; hg19: chr1-8412935; COSMIC: COSV61939008; COSMIC: COSV61939008;