ENST00000519685.5:c.56+1240C>T

Variant names:

• chr8-22995879-C-T
• rs750617453
• ENST00000519685.5:c.56+1240C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.74

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]

ENSG00000245025 (HGNC:58239):

LOC107984124 (HGNC:):

ACMG classification

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
RHOBTB2	NM_001160037.2	c.8C>T	p.Ala3Val	missense_variant	Exon 1 of 10		NP_001153509.1
RHOBTB2	NM_001160036.2	c.56+1240C>T		intron_variant	Intron 3 of 11		NP_001153508.1
RHOBTB2	XM_047421607.1	c.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
RHOBTB2	ENST00000519685.5	c.56+1240C>T		intron_variant	Intron 3 of 11	1		ENSP00000427926.1
RHOBTB2	ENST00000522948.5	c.8C>T	p.Ala3Val	missense_variant	Exon 1 of 10	5		ENSP00000429141.1
RHOBTB2	ENST00000524077.5	c.56+1240C>T		intron_variant	Intron 3 of 5	3		ENSP00000430785.1

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

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

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

Other links and lift over

dbSNP: rs750617453; hg19: chr8-22853392;