Genetic Variant NM_001042681.2:c.3568_3573dupAAGGAG (chr1-8359808-G-GCTCCTT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.32

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.3568_3573dupAAGGAG	p.Glu1191_Arg1192insLysGlu	conservative_inframe_insertion	Exon 19 of 23	ENST00000400908.7	NP_001036146.1	Q9P2R6-1
RERE	NM_012102.4 link	c.3568_3573dupAAGGAG	p.Glu1191_Arg1192insLysGlu	conservative_inframe_insertion	Exon 20 of 24		NP_036234.3	Q9P2R6-1
RERE	NM_001042682.2 link	c.1906_1911dupAAGGAG	p.Glu637_Arg638insLysGlu	conservative_inframe_insertion	Exon 9 of 13		NP_001036147.1	Q9P2R6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7 link	c.3568_3573dupAAGGAG	p.Glu1191_Arg1192insLysGlu	conservative_inframe_insertion	Exon 19 of 23	1	NM_001042681.2	ENSP00000383700.2		Q9P2R6-1

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1947

AN:

151640

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00308

AC XY:

408

AN XY:

132498

show subpopulations

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.:

Cov.:

AF XY:

0.00144

AC XY:

1043

AN XY:

723170

show subpopulations

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.:

Cov.:

AF XY:

0.0127

AC XY:

939

AN XY:

74164

show subpopulations

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

LINK: link

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over