rs149900041

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001042681.2(RERE):​c.1964C>T​(p.Ala655Val) variant causes a missense change. The variant allele was found at a frequency of 0.000399 in 1,614,102 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

RERE
NM_001042681.2 missense

Scores

2
3
14

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 6.99
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.047510624).
BP6
Variant 1-8361815-G-A is Benign according to our data. Variant chr1-8361815-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 377206.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr1-8361815-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00023 (35/152348) while in subpopulation NFE AF= 0.000426 (29/68032). AF 95% confidence interval is 0.000304. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RERENM_001042681.2 linkuse as main transcriptc.1964C>T p.Ala655Val missense_variant 17/23 ENST00000400908.7 NP_001036146.1 Q9P2R6-1
RERENM_012102.4 linkuse as main transcriptc.1964C>T p.Ala655Val missense_variant 18/24 NP_036234.3 Q9P2R6-1
RERENM_001042682.2 linkuse as main transcriptc.302C>T p.Ala101Val missense_variant 7/13 NP_001036147.1 Q9P2R6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
REREENST00000400908.7 linkuse as main transcriptc.1964C>T p.Ala655Val missense_variant 17/231 NM_001042681.2 ENSP00000383700.2 Q9P2R6-1

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.000426
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000231
AC:
58
AN:
251408
Hom.:
0
AF XY:
0.000162
AC XY:
22
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000174
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:
0.000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000417
AC:
609
AN:
1461754
Hom.:
0
Cov.:
31
AF XY:
0.000429
AC XY:
312
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000112
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:
0.000518
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152348
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000472
Hom.:
0
Bravo
AF:
0.000193
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000313
AC:
38
EpiCase
AF:
0.000545
EpiControl
AF:
0.000533

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:5
Uncertain significance, criteria provided, single submitterclinical testingInstitute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU DresdenNov 03, 2021- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 17, 2023- -
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsNov 11, 2016- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2024RERE: BP4, BS1 -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.17
T;.;.;T;.
Eigen
Benign
0.058
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
.;D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.048
T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.7
L;.;.;L;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.63
N;N;N;N;N
REVEL
Benign
0.069
Sift
Benign
0.29
T;T;T;T;T
Sift4G
Benign
0.18
T;T;T;T;.
Polyphen
0.0010
B;B;.;B;.
Vest4
0.49
MVP
0.20
MPC
0.52
ClinPred
0.055
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.075
gMVP
0.30

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.

Other links and lift over

dbSNP: rs149900041; hg19: chr1-8421875; API