Variant 6-7182047-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001003699.4(RREB1):c.136C>T(p.Pro46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,614,006 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

RREB1
NM_001003699.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.81

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048724413).

BP6

Variant 6-7182047-C-T is Benign according to our data. Variant chr6-7182047-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 740171.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RREB1	NM_001003699.4 link	c.136C>T	p.Pro46Ser	missense_variant	4/13	ENST00000379938.7	NP_001003699.1	Q92766-2
RREB1	NM_001003698.4 link	c.136C>T	p.Pro46Ser	missense_variant	4/12		NP_001003698.1	Q92766-1A0A024QZU8
RREB1	NM_001168344.2 link	c.136C>T	p.Pro46Ser	missense_variant	4/12		NP_001161816.1	Q92766-1A0A024QZU8
RREB1	NM_001003700.2 link	c.136C>T	p.Pro46Ser	missense_variant	4/12		NP_001003700.1	Q92766-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RREB1	ENST00000379938.7 link	c.136C>T	p.Pro46Ser	missense_variant	4/13	1	NM_001003699.4	ENSP00000369270.2		Q92766-2

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

189

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00416

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000366

AC:

AN:

251208

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00480

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:

0.0000528

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000156

AC:

228

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00436

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.00128

AC:

194

AN:

152152

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00427

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000167

Hom.:

Bravo

AF:

0.00136

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.010

T;T;.;.;.;T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.87

.;D;D;D;D;D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0049

T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;.;N;.;N;N;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.54

T;T;T;T;T;T;T

Sift4G

Benign

0.66

T;T;T;T;T;T;T

Polyphen

0.076

B;.;B;.;B;B;.

Vest4

0.24

MVP

0.39

MPC

0.60

ClinPred

0.011

GERP RS

4.0

Varity_R

0.092

gMVP

0.38

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