Variant 8-22994583-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000519685.5(RHOBTB2):c.-1G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 1,550,398 control chromosomes in the GnomAD database, including 2,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 573 hom., cov: 33)

Exomes 𝑓: 0.050 ( 1972 hom. )

Consequence

RHOBTB2
ENST00000519685.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.751

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:

(HGNC:):

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-22994583-G-A is Benign according to our data. Variant chr8-22994583-G-A is described in ClinVar as [Benign]. Clinvar id is 1265036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107984124	XR_007060857.1 linkuse as main transcript	n.127+5096C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000523884.1 linkuse as main transcript	n.149-9665C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11803

AN:

152066

Hom.:

568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.0325

Gnomad FIN

AF:

0.0874

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0485

Gnomad OTH

AF:

0.0656

GnomAD3 exomes

AF:

0.0610

AC:

9390

AN:

154028

Hom.:

400

AF XY:

0.0557

AC XY:

4549

AN XY:

81730

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.0463

Gnomad EAS exome

AF:

0.00404

Gnomad SAS exome

AF:

0.0326

Gnomad FIN exome

AF:

0.0829

Gnomad NFE exome

AF:

0.0446

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0496

AC:

69316

AN:

1398214

Hom.:

1972

Cov.:

AF XY:

0.0484

AC XY:

33377

AN XY:

689692

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.0448

Gnomad4 EAS exome

AF:

0.00246

Gnomad4 SAS exome

AF:

0.0334

Gnomad4 FIN exome

AF:

0.0791

Gnomad4 NFE exome

AF:

0.0466

Gnomad4 OTH exome

AF:

0.0498

GnomAD4 genome

AF:

0.0777

AC:

11825

AN:

152184

Hom.:

573

Cov.:

AF XY:

0.0798

AC XY:

5940

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.00502

Gnomad4 SAS

AF:

0.0325

Gnomad4 FIN

AF:

0.0874

Gnomad4 NFE

AF:

0.0485

Gnomad4 OTH

AF:

0.0644

Alfa

AF:

0.0585

Hom.:

149

Bravo

AF:

0.0810

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 18, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

RHOBTB2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2019

This variant is classified as 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_noAF

Benign

-0.82

CADD

Benign

1.5

DANN

Benign

0.64

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