1-8509847-C-T

Position:

• chr1-8509847-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.831-1172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,098 control chromosomes in the GnomAD database, including 26,825 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 0.59 (26825 hom., cov: 32)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

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 = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RERE	NM_001042681.2	c.831-1172G>A		intron_variant		ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.831-1172G>A		intron_variant			NP_036234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.831-1172G>A		intron_variant		1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89262 AN: 151980 Hom.: 26814 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.587 AC: 89316 AN: 152098 Hom.: 26825 Cov.: 32 AF XY: 0.592 AC XY: 44014 AN XY: 74342

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.534

Alfa AF: 0.597 Hom.: 14424

Bravo AF: 0.577

Asia WGS AF: 0.650 AC: 2260 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	0.21
DANN	Benign	0.25

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: rs11121194; hg19: chr1-8569906;