Genetic Variant RERE:c.*2212G>A (chr1-8352875-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001042681.2(RERE):c.*2212G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,438 control chromosomes in the GnomAD database, including 16,886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16846 hom., cov: 33)

Exomes 𝑓: 0.44 ( 40 hom. )

Consequence

RERE
NM_001042681.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder with or without congenital anomalies
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with or without anomalies of the brain, eye, or heart
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

RERE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RERE	NM_001042681.2 link	c.*2212G>A	3_prime_UTR_variant	Exon 23 of 23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4 link	c.*2212G>A	3_prime_UTR_variant	Exon 24 of 24		NP_036234.3
RERE	NM_001042682.2 link	c.*2212G>A	3_prime_UTR_variant	Exon 13 of 13		NP_001036147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7 link	c.*2212G>A		3_prime_UTR_variant	Exon 23 of 23	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69369

AN:

151962

Hom.:

16832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.481

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.444

AC:

159

AN:

358

Hom.:

Cov.:

AF XY:

0.398

AC XY:

AN XY:

206

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.451

AC:

155

AN:

344

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.300

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.456

AC:

69410

AN:

152080

Hom.:

16846

Cov.:

AF XY:

0.459

AC XY:

34099

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.329

AC:

13629

AN:

41478

American (AMR)

AF:

0.562

AC:

8578

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1718

AN:

3470

East Asian (EAS)

AF:

0.848

AC:

4392

AN:

5182

South Asian (SAS)

AF:

0.442

AC:

2131

AN:

4818

European-Finnish (FIN)

AF:

0.446

AC:

4714

AN:

10574

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.481

AC:

32726

AN:

67978

Other (OTH)

AF:

0.471

AC:

994

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1876

3753

5629

7506

9382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.477

Hom.:

58138

Bravo

AF:

0.464

Asia WGS

AF:

0.573

AC:

1994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.025

(source)

DANN

Benign

0.74

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over