rs10492963

Variant names:

• chr1-8750282-C-T
• rs10492963
• NM_001042681.2:c.-145+66878G>A

Variant summary

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

The NM_012102.4(RERE):​c.-145+42122G>A 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 524,422 control chromosomes in the GnomAD database, including 14,175 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 0.20 (3517 hom., cov: 31)
  • Exomes 𝑓: 0.23 (10658 hom.)
• Consequence: RERE NM_012102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 6 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]

RPL7P11 (HGNC:35667): (ribosomal protein L7 pseudogene 11)

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 (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012102.4. 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.-145+66878G>A		intron	N/A	NP_001036146.1
	RERE	NM_012102.4		c.-145+42122G>A		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.-145+66878G>A		intron	N/A	ENSP00000383700.2
	RERE	ENST00000337907.7	TSL:1	c.-145+42122G>A		intron	N/A	ENSP00000338629.3
	RERE	ENST00000864419.1		c.-145+3480G>A		intron	N/A	ENSP00000534478.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30521 AN: 151808 Hom.: 3517 Cov.: 31

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.231 AC: 86166 AN: 372498 Hom.: 10658 AF XY: 0.232 AC XY: 45842 AN XY: 197996

African (AFR) AF: 0.0927 AC: 1000 AN: 10790

American (AMR) AF: 0.249 AC: 3765 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 3503 AN: 11316

East Asian (EAS) AF: 0.124 AC: 3004 AN: 24204

South Asian (SAS) AF: 0.223 AC: 8840 AN: 39722

European-Finnish (FIN) AF: 0.203 AC: 4628 AN: 22754

Middle Eastern (MID) AF: 0.305 AC: 484 AN: 1586

European-Non Finnish (NFE) AF: 0.247 AC: 55783 AN: 225492

Other (OTH) AF: 0.240 AC: 5159 AN: 21508

GnomAD4 genome AF: 0.201 AC: 30524 AN: 151924 Hom.: 3517 Cov.: 31 AF XY: 0.200 AC XY: 14869 AN XY: 74234

African (AFR) AF: 0.0916 AC: 3801 AN: 41476

American (AMR) AF: 0.253 AC: 3859 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3470

East Asian (EAS) AF: 0.123 AC: 637 AN: 5172

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4824

European-Finnish (FIN) AF: 0.208 AC: 2178 AN: 10490

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.248 AC: 16866 AN: 67944

Other (OTH) AF: 0.263 AC: 551 AN: 2098

Alfa AF: 0.240 Hom.: 2640

Bravo AF: 0.201

Asia WGS AF: 0.202 AC: 701 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	1.1
DANN	Benign	0.74
PhyloP100		-1.1
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: rs10492963; hg19: chr1-8810341;