NM_001042681.2:c.1285-21688G>A

Variant names:

• chr1-8387662-C-T
• rs2120461
• NM_001042681.2:c.1285-21688G>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.1285-21688G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,000 control chromosomes in the GnomAD database, including 35,951 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 0.68 (35951 hom., cov: 32)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042681.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERE	NM_001042681.2	MANE Select	c.1285-21688G>A		intron	N/A	NP_001036146.1
	RERE	NM_012102.4		c.1285-21688G>A		intron	N/A	NP_036234.3
	RERE	NM_001042682.2		c.-378-21688G>A		intron	N/A	NP_001036147.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERE	ENST00000400908.7	TSL:1 MANE Select	c.1285-21688G>A		intron	N/A	ENSP00000383700.2
	RERE	ENST00000337907.7	TSL:1	c.1285-21688G>A		intron	N/A	ENSP00000338629.3
	RERE	ENST00000476556.5	TSL:1	c.-378-21688G>A		intron	N/A	ENSP00000422246.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103873 AN: 151882 Hom.: 35916 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.684 AC: 103962 AN: 152000 Hom.: 35951 Cov.: 32 AF XY: 0.685 AC XY: 50886 AN XY: 74304

African (AFR) AF: 0.629 AC: 26039 AN: 41408

American (AMR) AF: 0.764 AC: 11681 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2834 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4728 AN: 5188

South Asian (SAS) AF: 0.790 AC: 3800 AN: 4812

European-Finnish (FIN) AF: 0.621 AC: 6544 AN: 10542

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46059 AN: 67978

Other (OTH) AF: 0.726 AC: 1530 AN: 2108

Alfa AF: 0.671 Hom.: 12955

Bravo AF: 0.693

Asia WGS AF: 0.787 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.58
PhyloP100		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2120461; hg19: chr1-8447722; COSMIC: COSV61939080;