Variant 1-8355567-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001042681.2(RERE):c.4519A>G(p.Ile1507Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,598,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

RERE
NM_001042681.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.75

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17993486).

BP6

Variant 1-8355567-T-C is Benign according to our data. Variant chr1-8355567-T-C is described in ClinVar as [Benign]. Clinvar id is 2150683.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000201 (291/1446790) while in subpopulation NFE AF= 0.000248 (274/1103056). AF 95% confidence interval is 0.000224. There are 0 homozygotes in gnomad4_exome. There are 143 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RERE	NM_001042681.2 linkuse as main transcript	c.4519A>G	p.Ile1507Val	missense_variant	22/23	ENST00000400908.7
RERE	NM_012102.4 linkuse as main transcript	c.4519A>G	p.Ile1507Val	missense_variant	23/24
RERE	NM_001042682.2 linkuse as main transcript	c.2857A>G	p.Ile953Val	missense_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7 linkuse as main transcript	c.4519A>G	p.Ile1507Val	missense_variant	22/23	1	NM_001042681.2	P1	Q9P2R6-1

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.000192

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.0000734

AC:

AN:

231612

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

127068

show subpopulations

Gnomad AFR exome

AF:

0.0000689

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000148

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000201

AC:

291

AN:

1446790

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

143

AN XY:

717680

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000682

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000248

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.000106

AC:

AN:

151414

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73946

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.000253

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000581

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.;.;T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

.;D;D;D;D;D

M_CAP

Benign

0.0094

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

M;.;.;.;M;.

MutationTaster

Benign

0.99

D;D;D;D;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.61

N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0040

D;D;T;D;D;D

Sift4G

Uncertain

0.0080

D;T;T;D;D;.

Polyphen

0.85

P;.;.;.;P;.

Vest4

0.36

MVP

0.40

MPC

0.30

ClinPred

0.13

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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