8-22994583-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.751

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]

(HGNC:):

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]

ACMG classification

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	UniProt
LOC107984124	XR_007060857.1	n.127+5096C>T		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11803 AN: 152066 Hom.: 568 Cov.: 33

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

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.: 30 AF XY: 0.0484 AC XY: 33377 AN XY: 689692

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.: 33 AF XY: 0.0798 AC XY: 5940 AN XY: 74398

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

RHOBTB2-related disorder Benign:1

Benign, criteria provided, single submitter

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2020

- -

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

Other links and lift over

dbSNP: rs78886842; hg19: chr8-22852096;