Variant 6-7189168-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000379938.7(RREB1):c.271G>A(p.Asp91Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RREB1
ENST00000379938.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RREB1	NM_001003699.4 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	6/13	ENST00000379938.7	NP_001003699.1
RREB1	NM_001003698.4 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	6/12		NP_001003698.1
RREB1	NM_001168344.2 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	6/12		NP_001161816.1
RREB1	NM_001003700.2 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	6/12		NP_001003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RREB1	ENST00000379938.7 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	6/13	1	NM_001003699.4	ENSP00000369270	P1	Q92766-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249318

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.271G>A (p.D91N) alteration is located in exon 6 (coding exon 3) of the RREB1 gene. This alteration results from a G to A substitution at nucleotide position 271, causing the aspartic acid (D) at amino acid position 91 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

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

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

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

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.54

D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;L;.;L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.4

D;D;D;D;D;D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

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

Vest4

0.73

MVP

0.70

MPC

1.4

ClinPred

0.97

GERP RS

5.7

Varity_R

0.52

gMVP

0.45

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