chr8-22994608-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PM1PM2BP4_StrongBP6_Moderate

The NM_001160036.2(RHOBTB2):c.25G>A(p.Asp9Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,551,470 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000050 ( 1 hom. )

Consequence

RHOBTB2
NM_001160036.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.711

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 -2 ACMG points.

PM1

In a region_of_interest Rho-like (size 209) in uniprot entity RHBT2_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001160036.2

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052758098).

BP6

Variant 8-22994608-G-A is Benign according to our data. Variant chr8-22994608-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2812682.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
RHOBTB2	NM_001160036.2 link	c.25G>A	p.Asp9Asn	missense_variant	Exon 3 of 12	NP_001153508.1	Q9BYZ6-2
RHOBTB2	XM_047421607.1 link	c.25G>A	p.Asp9Asn	missense_variant	Exon 3 of 12	XP_047277563.1
RHOBTB2	XM_047421608.1 link	c.25G>A	p.Asp9Asn	missense_variant	Exon 3 of 12	XP_047277564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
RHOBTB2	ENST00000519685.5 link	c.25G>A	p.Asp9Asn	missense_variant	Exon 3 of 12	1	ENSP00000427926.1	Q9BYZ6-2
RHOBTB2	ENST00000524077.5 link	c.25G>A	p.Asp9Asn	missense_variant	Exon 3 of 6	3	ENSP00000430785.1	E5RI44
PEBP4	ENST00000522278.1 link	c.144+5071C>T		intron_variant	Intron 1 of 1	5	ENSP00000429414.1	E5RIK3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1399292

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.3

DANN

Benign

0.44

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.0060

Sift

Benign

0.92

T;T

Sift4G

Benign

0.98

T;T

Vest4

0.13

MutPred

0.19

Loss of ubiquitination at K13 (P = 0.0211);Loss of ubiquitination at K13 (P = 0.0211);

MVP

0.45

MPC

1.3

ClinPred

0.024

GERP RS

-1.8

gMVP

0.26

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