1-8699495-T-C

Position:

• chr1-8699495-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RERE	NM_001042681.2	c.-144-43054A>G		intron_variant		ENST00000400908.7
RERE	NM_012102.4	c.-144-43054A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.-144-43054A>G		intron_variant		1	NM_001042681.2	P1

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.256

Alfa AF: 0.285 Hom.: 7455

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12025126; hg19: chr1-8759554;