1-8429242-C-T

Variant names:

• chr1-8429242-C-T
• rs301799
• NM_001042681.2:c.1204-6435G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042681.2(RERE):​c.1204-6435G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,956 control chromosomes in the GnomAD database, including 28,764 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 0.61 (28764 hom., cov: 31)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 42 publications found

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]

RERE-AS1 (HGNC:40501): (RERE antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.1204-6435G>A		intron_variant	Intron 11 of 22	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.1204-6435G>A		intron_variant	Intron 12 of 23		NP_036234.3
RERE-AS1	NR_125999.1	n.165-585C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.1204-6435G>A		intron_variant	Intron 11 of 22	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92431 AN: 151838 Hom.: 28736 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.609 AC: 92517 AN: 151956 Hom.: 28764 Cov.: 31 AF XY: 0.613 AC XY: 45555 AN XY: 74294

African (AFR) AF: 0.674 AC: 27896 AN: 41410

American (AMR) AF: 0.615 AC: 9384 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1403 AN: 3470

East Asian (EAS) AF: 0.829 AC: 4292 AN: 5178

South Asian (SAS) AF: 0.487 AC: 2344 AN: 4816

European-Finnish (FIN) AF: 0.672 AC: 7089 AN: 10556

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38317 AN: 67950

Other (OTH) AF: 0.546 AC: 1150 AN: 2108

Alfa AF: 0.593 Hom.: 8533

Bravo AF: 0.610

Asia WGS AF: 0.647 AC: 2249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.17
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs301799; hg19: chr1-8489302;