rs4908760

Variant names:

• chr1-8466082-G-A
• rs4908760
• NM_001042681.2:c.1105-59C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-8466082-G-A
• chr1-8466082-G-C
• chr1-8466082-G-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.1105-59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,389,238 control chromosomes in the GnomAD database, including 286,425 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 0.67 (35486 hom., cov: 30)
  • Exomes 𝑓: 0.63 (250939 hom.)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• Publications: 45 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 (EAS) allele frequency at 95% confidence interval = 0.812 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERE	NM_001042681.2	MANE Select	c.1105-59C>T		intron	N/A	NP_001036146.1
	RERE	NM_012102.4		c.1105-59C>T		intron	N/A	NP_036234.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERE	ENST00000400908.7	TSL:1 MANE Select	c.1105-59C>T		intron	N/A	ENSP00000383700.2
	RERE	ENST00000337907.7	TSL:1	c.1105-59C>T		intron	N/A	ENSP00000338629.3
	RERE	ENST00000377464.5	TSL:5	c.301-59C>T		intron	N/A	ENSP00000366684.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102342 AN: 151852 Hom.: 35438 Cov.: 30

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.632 AC: 782108 AN: 1237268 Hom.: 250939 AF XY: 0.627 AC XY: 384712 AN XY: 613598

African (AFR) AF: 0.812 AC: 23360 AN: 28762

American (AMR) AF: 0.635 AC: 21817 AN: 34338

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 8866 AN: 20906

East Asian (EAS) AF: 0.839 AC: 31750 AN: 37836

South Asian (SAS) AF: 0.536 AC: 38683 AN: 72148

European-Finnish (FIN) AF: 0.704 AC: 33874 AN: 48108

Middle Eastern (MID) AF: 0.386 AC: 1743 AN: 4516

European-Non Finnish (NFE) AF: 0.629 AC: 589884 AN: 938480

Other (OTH) AF: 0.616 AC: 32131 AN: 52174

GnomAD4 genome AF: 0.674 AC: 102451 AN: 151970 Hom.: 35486 Cov.: 30 AF XY: 0.677 AC XY: 50274 AN XY: 74266

African (AFR) AF: 0.810 AC: 33577 AN: 41478

American (AMR) AF: 0.614 AC: 9364 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4308 AN: 5170

South Asian (SAS) AF: 0.534 AC: 2567 AN: 4808

European-Finnish (FIN) AF: 0.704 AC: 7418 AN: 10532

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41835 AN: 67950

Other (OTH) AF: 0.599 AC: 1263 AN: 2110

Alfa AF: 0.624 Hom.: 132284

Bravo AF: 0.675

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.38
PhyloP100		0.75
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: rs4908760; hg19: chr1-8526142;