1-8556779-T-G

Variant names:

• chr1-8556779-T-G
• rs1473420
• NM_001042681.2:c.629-208A>C

Variant summary

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

The NM_001042681.2(RERE):​c.629-208A>C 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 151,962 control chromosomes in the GnomAD database, including 26,776 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 (26776 hom., cov: 31)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 11 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

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 = 0.814 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.629-208A>C		intron	N/A	NP_001036146.1	Q9P2R6-1
	RERE	NM_012102.4		c.629-208A>C		intron	N/A	NP_036234.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERE	ENST00000400908.7	TSL:1 MANE Select	c.629-208A>C		intron	N/A	ENSP00000383700.2	Q9P2R6-1
	RERE	ENST00000337907.7	TSL:1	c.629-208A>C		intron	N/A	ENSP00000338629.3	Q9P2R6-1
	RERE	ENST00000864419.1		c.629-208A>C		intron	N/A	ENSP00000534478.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89128 AN: 151844 Hom.: 26765 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.509

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: 89183 AN: 151962 Hom.: 26776 Cov.: 31 AF XY: 0.591 AC XY: 43925 AN XY: 74282

African (AFR) AF: 0.509 AC: 21093 AN: 41440

American (AMR) AF: 0.584 AC: 8923 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3468

East Asian (EAS) AF: 0.835 AC: 4317 AN: 5170

South Asian (SAS) AF: 0.507 AC: 2443 AN: 4814

European-Finnish (FIN) AF: 0.703 AC: 7415 AN: 10550

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

European-Non Finnish (NFE) AF: 0.615 AC: 41763 AN: 67938

Other (OTH) AF: 0.533 AC: 1122 AN: 2104

Alfa AF: 0.583 Hom.: 13135

Bravo AF: 0.578

Asia WGS AF: 0.641 AC: 2229 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	0.16
DANN	Benign	0.71
PhyloP100		-1.7
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: rs1473420; hg19: chr1-8616838; COSMIC: COSV61951637;