1-8469081-T-C

Variant names:

• chr1-8469081-T-C
• rs751790
• NM_001042681.2:c.1105-3058A>G

Variant summary

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

The NM_001042681.2(RERE):​c.1105-3058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,914 control chromosomes in the GnomAD database, including 2,417 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 (2417 hom., cov: 31)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 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.1105-3058A>G		intron	N/A	NP_001036146.1
	RERE	NM_012102.4		c.1105-3058A>G		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.1105-3058A>G		intron	N/A	ENSP00000383700.2
	RERE	ENST00000337907.7	TSL:1	c.1105-3058A>G		intron	N/A	ENSP00000338629.3
	RERE	ENST00000377464.5	TSL:5	c.301-3058A>G		intron	N/A	ENSP00000366684.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25521 AN: 151796 Hom.: 2415 Cov.: 31

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.168 AC: 25530 AN: 151914 Hom.: 2417 Cov.: 31 AF XY: 0.167 AC XY: 12428 AN XY: 74250

African (AFR) AF: 0.0872 AC: 3612 AN: 41422

American (AMR) AF: 0.232 AC: 3544 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3468

East Asian (EAS) AF: 0.110 AC: 571 AN: 5176

South Asian (SAS) AF: 0.171 AC: 822 AN: 4818

European-Finnish (FIN) AF: 0.171 AC: 1801 AN: 10516

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13555 AN: 67940

Other (OTH) AF: 0.221 AC: 465 AN: 2106

Alfa AF: 0.187 Hom.: 641

Bravo AF: 0.171

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		-1.2
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: rs751790; hg19: chr1-8529141; COSMIC: COSV61939205;