chr1-8699495-T-C

Variant names:

• chr1-8699495-T-C
• rs12025126
• NM_001042681.2:c.-144-43054A>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.-144-43054A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,132 control chromosomes in the GnomAD database, including 6,617 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 0.27 (6617 hom., cov: 32)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 19 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.-144-43054A>G		intron_variant	Intron 1 of 22	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.-144-43054A>G		intron_variant	Intron 2 of 23		NP_036234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.-144-43054A>G		intron_variant	Intron 1 of 22	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40533 AN: 152014 Hom.: 6610 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.267 AC: 40554 AN: 152132 Hom.: 6617 Cov.: 32 AF XY: 0.274 AC XY: 20386 AN XY: 74360

African (AFR) AF: 0.144 AC: 5984 AN: 41528

American (AMR) AF: 0.375 AC: 5734 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.770 AC: 3983 AN: 5176

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3480 AN: 10554

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18547 AN: 67978

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.278 Hom.: 18382

Bravo AF: 0.269

Asia WGS AF: 0.443 AC: 1541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.80
PhyloP100		-1.4
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: rs12025126; hg19: chr1-8759554;