rs754336279

Variant names:

• chr1-8359808-GCTCCTTCTCCTT-G
• rs147985313
• NM_001042681.2:c.3562_3573delAAGGAGAAGGAG

Your query was ambiguous. Multiple possible variants found:

• chr1-8359808-GCTCCTTCTCCTT-G
• chr1-8359808-GCTCCTT-G
• chr1-8359808-G-GCTCCTTCTCCTT
• chr1-8359808-G-GCTCCTT

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001042681.2(RERE):​c.3562_3573delAAGGAGAAGGAG​(p.Lys1188_Glu1191del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,604,454 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: RERE NM_001042681.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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 Likely_benign. Variant got -3 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BS2: High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.3562_3573delAAGGAGAAGGAG	p.Lys1188_Glu1191del	conservative_inframe_deletion	Exon 19 of 23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.3562_3573delAAGGAGAAGGAG	p.Lys1188_Glu1191del	conservative_inframe_deletion	Exon 20 of 24		NP_036234.3
RERE	NM_001042682.2	c.1900_1911delAAGGAGAAGGAG	p.Lys634_Glu637del	conservative_inframe_deletion	Exon 9 of 13		NP_001036147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.3562_3573delAAGGAGAAGGAG	p.Lys1188_Glu1191del	conservative_inframe_deletion	Exon 19 of 23	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151650 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000282 AC: 41 AN: 1452804 Hom.: 0 AF XY: 0.0000332 AC XY: 24 AN XY: 723170

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151650 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74044

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Apr 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.3562_3573del, results in the deletion of 4 amino acid(s) of the RERE protein (p.Lys1188_Glu1191del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RERE-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147985313; hg19: chr1-8419868;