ENST00000519685.5:c.56+1240C>A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The ENST00000519685.5(RHOBTB2):c.56+1240C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000419 in 1,551,374 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

RHOBTB2
ENST00000519685.5 intron

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.74

Variant links:

Genes affected

RHOBTB2 (HGNC:18756): (Rho related BTB domain containing 2) The protein encoded by this gene is a small Rho GTPase and a candidate tumor suppressor. The encoded protein interacts with the cullin-3 protein, a ubiquitin E3 ligase necessary for mitotic cell division. This protein inhibits the growth and spread of some types of breast cancer. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

RHOBTB2 links:

PEBP4 (HGNC:28319): (phosphatidylethanolamine binding protein 4) The phosphatidylethanolamine (PE)-binding proteins, including PEBP4, are an evolutionarily conserved family of proteins with pivotal biologic functions, such as lipid binding and inhibition of serine proteases (Wang et al., 2004 [PubMed 15302887]).[supplied by OMIM, Dec 2008]

PEBP4 links:

ENSG00000245025 (HGNC:58239):

ENSG00000245025 links:

LOC107984124 (HGNC:):

LOC107984124 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007869661).

BP6

Variant 8-22995879-C-A is Benign according to our data. Variant chr8-22995879-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3054504.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
RHOBTB2	NM_001160037.2 link	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 10	NP_001153509.1	Q9BYZ6-3
RHOBTB2	NM_001160036.2 link	c.56+1240C>A		intron_variant	Intron 3 of 11	NP_001153508.1	Q9BYZ6-2
RHOBTB2	XM_047421607.1 link	c.56+1240C>A		intron_variant	Intron 3 of 11	XP_047277563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
RHOBTB2	ENST00000519685.5 link	c.56+1240C>A		intron_variant	Intron 3 of 11	1	ENSP00000427926.1	Q9BYZ6-2
RHOBTB2	ENST00000522948.5 link	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 10	5	ENSP00000429141.1	Q9BYZ6-3
RHOBTB2	ENST00000524077.5 link	c.56+1240C>A		intron_variant	Intron 3 of 5	3	ENSP00000430785.1	E5RI44

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000260

AC:

AN:

154102

Hom.:

AF XY:

0.000257

AC XY:

AN XY:

81772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00130

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:

0.00

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.0000400

AC:

AN:

1399238

Hom.:

Cov.:

AF XY:

0.0000362

AC XY:

AN XY:

690136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00140

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:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000366

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RHOBTB2-related disorder

Benign:1

Jan 19, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.032

DANN

Benign

0.48

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.26

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.010

REVEL

Benign

0.0050

Sift

Benign

0.046

Sift4G

Benign

0.070

Vest4

0.10

MutPred

0.29

Loss of MoRF binding (P = 0.0057);

MVP

0.093

ClinPred

0.072

GERP RS

-5.7

Splicing

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