dbSNP rs6931262: RREB1:n.7260C>T (chr6-7217284-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000475946.5(RREB1):n.7260C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,238 control chromosomes in the GnomAD database, including 1,606 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 0.10 ( 1606 hom., cov: 32)

Exomes 𝑓: 0.021 ( 0 hom. )

Consequence

RREB1
ENST00000475946.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Publications

20 publications found

Variant links:

Genes affected

RREB1 (HGNC:10449): (ras responsive element binding protein 1) The protein encoded by this gene is a zinc finger transcription factor that binds to RAS-responsive elements (RREs) of gene promoters. It has been shown that the calcitonin gene promoter contains an RRE and that the encoded protein binds there and increases expression of calcitonin, which may be involved in Ras/Raf-mediated cell differentiation. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

RREB1 Gene-Disease associations (from GenCC):

22q11.2 deletion syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

RREB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RREB1	NM_001003699.4 link	c.707+5575C>T	intron_variant	Intron 8 of 12	ENST00000379938.7	NP_001003699.1
RREB1	NM_001003698.4 link	c.707+5575C>T	intron_variant	Intron 8 of 11		NP_001003698.1
RREB1	NM_001168344.2 link	c.707+5575C>T	intron_variant	Intron 8 of 11		NP_001161816.1
RREB1	NM_001003700.2 link	c.707+5575C>T	intron_variant	Intron 8 of 11		NP_001003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RREB1	ENST00000379938.7 link	c.707+5575C>T		intron_variant	Intron 8 of 12	1	NM_001003699.4	ENSP00000369270.2

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15513

AN:

152072

Hom.:

1603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0540

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.0487

Gnomad FIN

AF:

0.0394

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0297

Gnomad OTH

AF:

0.0824

GnomAD4 exome

AF:

0.0208

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0385

AC XY:

AN XY:

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:

0.0625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.102

AC:

15542

AN:

152190

Hom.:

1606

Cov.:

AF XY:

0.101

AC XY:

7552

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.250

AC:

10356

AN:

41490

American (AMR)

AF:

0.0539

AC:

824

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0674

AC:

234

AN:

3470

East Asian (EAS)

AF:

0.240

AC:

1241

AN:

5174

South Asian (SAS)

AF:

0.0487

AC:

235

AN:

4822

European-Finnish (FIN)

AF:

0.0394

AC:

418

AN:

10598

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0297

AC:

2022

AN:

68024

Other (OTH)

AF:

0.0844

AC:

178

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

639

1278

1917

2556

3195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0533

Hom.:

1934

Bravo

AF:

0.109

Asia WGS

AF:

0.117

AC:

405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

0.20

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over