Genetic Variant ENST00000519685.5:c.56+1240C>T (chr8-22995879-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000519685.5(RHOBTB2):c.56+1240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,399,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RHOBTB2
ENST00000519685.5 intron

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04091069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
RHOBTB2	NM_001160037.2 link	c.8C>T	p.Ala3Val	missense_variant	Exon 1 of 10	NP_001153509.1	Q9BYZ6-3
RHOBTB2	NM_001160036.2 link	c.56+1240C>T		intron_variant	Intron 3 of 11	NP_001153508.1	Q9BYZ6-2
RHOBTB2	XM_047421607.1 link	c.56+1240C>T		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>T		intron_variant	Intron 3 of 11	1	ENSP00000427926.1	Q9BYZ6-2
RHOBTB2	ENST00000522948.5 link	c.8C>T	p.Ala3Val	missense_variant	Exon 1 of 10	5	ENSP00000429141.1	Q9BYZ6-3
RHOBTB2	ENST00000524077.5 link	c.56+1240C>T		intron_variant	Intron 3 of 5	3	ENSP00000430785.1	E5RI44

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000454

AC:

AN:

154102

Hom.:

AF XY:

0.0000367

AC XY:

AN XY:

81772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000183

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000502

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1399238

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000111

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.29

DANN

Benign

0.58

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.32

M_CAP

Benign

0.0032

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.070

REVEL

Benign

0.0040

Sift

Benign

0.045

Sift4G

Benign

0.12

Vest4

0.11

MutPred

0.29

Gain of sheet (P = 0.0073);

MVP

0.18

ClinPred

0.048

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over