rs1354008866

Variant names:

• chr8-22994625-C-A
• rs1354008866
• ENST00000519685.5:c.42C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22994625-C-A
• chr8-22994625-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001160036.2(RHOBTB2):​c.42C>A​(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RHOBTB2 NM_001160036.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=0.348 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOBTB2	NM_001160036.2	c.42C>A	p.Thr14Thr	synonymous_variant	Exon 3 of 12		NP_001153508.1
RHOBTB2	XM_047421607.1	c.42C>A	p.Thr14Thr	synonymous_variant	Exon 3 of 12		XP_047277563.1
RHOBTB2	XM_047421608.1	c.42C>A	p.Thr14Thr	synonymous_variant	Exon 3 of 12		XP_047277564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOBTB2	ENST00000519685.5	c.42C>A	p.Thr14Thr	synonymous_variant	Exon 3 of 12	1		ENSP00000427926.1
RHOBTB2	ENST00000524077.5	c.42C>A	p.Thr14Thr	synonymous_variant	Exon 3 of 6	3		ENSP00000430785.1
PEBP4	ENST00000522278.1	c.144+5054G>T		intron_variant	Intron 1 of 1	5		ENSP00000429414.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.4
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1354008866; hg19: chr8-22852138;