8-22995879-C-T

Variant summary

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

The NM_001160037.2(RHOBTB2):​c.8C>T​(p.Ala3Val) variant causes a missense 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. 12/15 in silico tools predict 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
NM_001160037.2 missense

Scores

16

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]
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]

Genome browser will be placed here

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 MANE Protein UniProt
RHOBTB2NM_001160037.2 linkc.8C>T p.Ala3Val missense_variant Exon 1 of 10 NP_001153509.1 Q9BYZ6-3
RHOBTB2NM_001160036.2 linkc.56+1240C>T intron_variant Intron 3 of 11 NP_001153508.1 Q9BYZ6-2
RHOBTB2XM_047421607.1 linkc.56+1240C>T intron_variant Intron 3 of 11 XP_047277563.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHOBTB2ENST00000519685.5 linkc.56+1240C>T intron_variant Intron 3 of 11 1 ENSP00000427926.1 Q9BYZ6-2
RHOBTB2ENST00000522948.5 linkc.8C>T p.Ala3Val missense_variant Exon 1 of 10 5 ENSP00000429141.1 Q9BYZ6-3
RHOBTB2ENST00000524077.5 linkc.56+1240C>T intron_variant Intron 3 of 5 3 ENSP00000430785.1 E5RI44

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000454
AC:
7
AN:
154102
Hom.:
0
AF XY:
0.0000367
AC XY:
3
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:
18
AN:
1399238
Hom.:
0
Cov.:
30
AF XY:
0.00000580
AC XY:
4
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.:
33
Alfa
AF:
0.0000450
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.53
T
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
N
LIST_S2
Benign
0.32
T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.041
T
MetaSVM
Benign
-0.95
T
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.070
N
REVEL
Benign
0.0040
Sift
Benign
0.045
D
Sift4G
Benign
0.12
T
Vest4
0.11
MutPred
0.29
Gain of sheet (P = 0.0073);
MVP
0.18
ClinPred
0.048
T
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.

Other links and lift over

dbSNP: rs750617453; hg19: chr8-22853392; API