Variant 1-8656247-T-TCGGTCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

The NM_001042681.2(RERE):c.50_51insGGACCG(p.Asp20_Arg21dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00874 in 1,613,208 control chromosomes in the GnomAD database, including 81 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0090 ( 77 hom. )

Consequence

RERE
NM_001042681.2 inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 6.80

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001042681.2.

BP6

Variant 1-8656247-T-TCGGTCC is Benign according to our data. Variant chr1-8656247-T-TCGGTCC is described in ClinVar as [Benign]. Clinvar id is 377359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00628 (955/152186) while in subpopulation NFE AF= 0.00947 (644/67990). AF 95% confidence interval is 0.00887. There are 4 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 955 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RERE	NM_001042681.2 linkuse as main transcript	c.50_51insGGACCG	p.Asp20_Arg21dup	inframe_insertion	2/23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4 linkuse as main transcript	c.50_51insGGACCG	p.Asp20_Arg21dup	inframe_insertion	3/24		NP_036234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7 linkuse as main transcript	c.50_51insGGACCG	p.Asp20_Arg21dup	inframe_insertion	2/23	1	NM_001042681.2	ENSP00000383700	P1	Q9P2R6-1

Frequencies

GnomAD3 genomes

AF:

0.00627

AC:

954

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00947

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00641

AC:

1607

AN:

250740

Hom.:

AF XY:

0.00664

AC XY:

901

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00281

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.00876

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00900

AC:

13149

AN:

1461022

Hom.:

Cov.:

AF XY:

0.00895

AC XY:

6504

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00306

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00734

GnomAD4 genome

AF:

0.00628

AC:

955

AN:

152186

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

482

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.00947

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00764

Hom.:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Nov 07, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	RERE: BS1, BS2 -

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