rs7523186

Variant names:

• chr1-8595436-A-G
• rs7523186
• NM_001042681.2:c.522+19125T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-8595436-A-G
• chr1-8595436-A-T

Variant summary

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

The ENST00000400908.7(RERE):​c.522+19125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,822 control chromosomes in the GnomAD database, including 3,897 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 0.22 (3897 hom., cov: 32)
• Consequence: RERE ENST00000400908.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000400908.7. 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.522+19125T>C		intron	N/A	NP_001036146.1
	RERE	NM_012102.4		c.522+19125T>C		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.522+19125T>C		intron	N/A	ENSP00000383700.2
	RERE	ENST00000337907.7	TSL:1	c.522+19125T>C		intron	N/A	ENSP00000338629.3
	RERE	ENST00000656437.1		c.522+19125T>C		intron	N/A	ENSP00000499322.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33737 AN: 151706 Hom.: 3885 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.223 AC: 33784 AN: 151822 Hom.: 3897 Cov.: 32 AF XY: 0.221 AC XY: 16397 AN XY: 74266

African (AFR) AF: 0.267 AC: 11093 AN: 41472

American (AMR) AF: 0.252 AC: 3842 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3464

East Asian (EAS) AF: 0.110 AC: 572 AN: 5178

South Asian (SAS) AF: 0.196 AC: 947 AN: 4826

European-Finnish (FIN) AF: 0.175 AC: 1816 AN: 10392

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13728 AN: 67922

Other (OTH) AF: 0.270 AC: 567 AN: 2102

Alfa AF: 0.212 Hom.: 531

Bravo AF: 0.232

Asia WGS AF: 0.177 AC: 609 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.94
DANN	Benign	0.65
PhyloP100		-0.35
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: rs7523186; hg19: chr1-8655495; COSMIC: COSV61939395; COSMIC: COSV61939395;