Variant chr1-8355571-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001042681.2(RERE):c.4515G>T(p.Gly1505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000887 in 1,599,088 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00092 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

RERE
NM_001042681.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.332

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 1-8355571-C-A is Benign according to our data. Variant chr1-8355571-C-A is described in ClinVar as [Benign]. Clinvar id is 1600804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000919 (140/152296) while in subpopulation AMR AF= 0.00176 (27/15304). AF 95% confidence interval is 0.00124. There are 1 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RERE	NM_001042681.2 linkuse as main transcript	c.4515G>T	p.Gly1505=	synonymous_variant	22/23	ENST00000400908.7
RERE	NM_012102.4 linkuse as main transcript	c.4515G>T	p.Gly1505=	synonymous_variant	23/24
RERE	NM_001042682.2 linkuse as main transcript	c.2853G>T	p.Gly951=	synonymous_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7 linkuse as main transcript	c.4515G>T	p.Gly1505=	synonymous_variant	22/23	1	NM_001042681.2	P1	Q9P2R6-1

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000869

AC:

200

AN:

230020

Hom.:

AF XY:

0.000919

AC XY:

116

AN XY:

126186

show subpopulations

Gnomad AFR exome

AF:

0.0000691

Gnomad AMR exome

AF:

0.000567

Gnomad ASJ exome

AF:

0.00324

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000446

Gnomad FIN exome

AF:

0.000600

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.000891

GnomAD4 exome

AF:

0.000884

AC:

1279

AN:

1446792

Hom.:

Cov.:

AF XY:

0.000932

AC XY:

669

AN XY:

717696

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000706

Gnomad4 ASJ exome

AF:

0.00271

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000353

Gnomad4 FIN exome

AF:

0.000607

Gnomad4 NFE exome

AF:

0.000952

Gnomad4 OTH exome

AF:

0.000955

GnomAD4 genome

AF:

0.000919

AC:

140

AN:

152296

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000879

Hom.:

Bravo

AF:

0.00102

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	RERE: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: -23

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