rs11121182

Variant names:

• chr1-8462493-C-A
• rs11121182
• NM_001042681.2:c.1203+3432G>T

Variant summary

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

The NM_001042681.2(RERE):​c.1203+3432G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,224 control chromosomes in the GnomAD database, including 2,411 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 0.17 (2411 hom., cov: 32)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.1203+3432G>T		intron_variant	Intron 11 of 22	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.1203+3432G>T		intron_variant	Intron 12 of 23		NP_036234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.1203+3432G>T		intron_variant	Intron 11 of 22	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25394 AN: 152106 Hom.: 2409 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.167 AC: 25401 AN: 152224 Hom.: 2411 Cov.: 32 AF XY: 0.166 AC XY: 12350 AN XY: 74452

African (AFR) AF: 0.0831 AC: 3452 AN: 41534

American (AMR) AF: 0.233 AC: 3559 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 792 AN: 3470

East Asian (EAS) AF: 0.109 AC: 564 AN: 5182

South Asian (SAS) AF: 0.171 AC: 827 AN: 4830

European-Finnish (FIN) AF: 0.171 AC: 1815 AN: 10608

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.200 AC: 13565 AN: 67990

Other (OTH) AF: 0.220 AC: 464 AN: 2112

Alfa AF: 0.198 Hom.: 4635

Bravo AF: 0.170

Asia WGS AF: 0.159 AC: 553 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	0.93
DANN	Benign	0.53
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11121182; hg19: chr1-8522553; COSMIC: COSV61939177; COSMIC: COSV61939177;