1-8509847-C-T

Variant names:

• chr1-8509847-C-T
• rs11121194
• NM_001042681.2:c.831-1172G>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.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
• Publications: 15 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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder with or without congenital anomalies

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with or without anomalies of the brain, eye, or heart

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.831-1172G>A		intron_variant	Intron 7 of 22	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.831-1172G>A		intron_variant	Intron 8 of 23		NP_036234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.831-1172G>A		intron_variant	Intron 7 of 22	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

African (AFR) AF: 0.508 AC: 21079 AN: 41470

American (AMR) AF: 0.582 AC: 8902 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1478 AN: 3472

East Asian (EAS) AF: 0.835 AC: 4320 AN: 5174

South Asian (SAS) AF: 0.527 AC: 2542 AN: 4820

European-Finnish (FIN) AF: 0.703 AC: 7441 AN: 10578

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41793 AN: 67988

Other (OTH) AF: 0.534 AC: 1124 AN: 2106

Alfa AF: 0.596 Hom.: 15912

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
PhyloP100		-2.3
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: rs11121194; hg19: chr1-8569906;