chr1-8359808-G-GCTCCTT

Variant names:

• chr1-8359808-G-GCTCCTT
• rs147985313
• NM_001042681.2:c.3568_3573dupAAGGAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001042681.2(RERE):​c.3568_3573dupAAGGAG​(p.Glu1191_Arg1192insLysGlu) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,604,560 control chromosomes in the GnomAD database, including 77 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (35 hom., cov: 30)
  • Exomes 𝑓: 0.0016 (42 hom.)
• Consequence: RERE NM_001042681.2 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.32

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 -16 ACMG points.

• BP6: Variant 1-8359808-G-GCTCCTT is Benign according to our data. Variant chr1-8359808-G-GCTCCTT is described in ClinVar as [Benign]. Clinvar id is 777879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1949/151758) while in subpopulation AFR AF= 0.0428 (1772/41398). AF 95% confidence interval is 0.0411. There are 35 homozygotes in gnomad4. There are 939 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1949 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.3568_3573dupAAGGAG	p.Glu1191_Arg1192insLysGlu	conservative_inframe_insertion	Exon 19 of 23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.3568_3573dupAAGGAG	p.Glu1191_Arg1192insLysGlu	conservative_inframe_insertion	Exon 20 of 24		NP_036234.3
RERE	NM_001042682.2	c.1906_1911dupAAGGAG	p.Glu637_Arg638insLysGlu	conservative_inframe_insertion	Exon 9 of 13		NP_001036147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.3568_3573dupAAGGAG	p.Glu1191_Arg1192insLysGlu	conservative_inframe_insertion	Exon 19 of 23	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1947 AN: 151640 Hom.: 35 Cov.: 30

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00697

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000486

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00396 AC: 962 AN: 243122 Hom.: 15 AF XY: 0.00308 AC XY: 408 AN XY: 132498

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.00398

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.000493

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000448

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00162 AC: 2355 AN: 1452802 Hom.: 42 Cov.: 33 AF XY: 0.00144 AC XY: 1043 AN XY: 723170

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.000880

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.000476

Gnomad4 FIN exome AF: 0.0000220

Gnomad4 NFE exome AF: 0.000347

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome AF: 0.0128 AC: 1949 AN: 151758 Hom.: 35 Cov.: 30 AF XY: 0.0127 AC XY: 939 AN XY: 74164

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.00696

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.00126

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000486

Gnomad4 OTH AF: 0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

See cases Benign:1

Feb 25, 2020

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG classification criteria: BS1, BS2 -

not provided Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart Benign:1

Jul 28, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;