8-22994530-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000519685.5(RHOBTB2):c.-23-31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,384,776 control chromosomes in the GnomAD database, including 9,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (974 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8610 hom.)
• Consequence: RHOBTB2 ENST00000519685.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.180

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]

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-22994530-C-T is Benign according to our data. Variant chr8-22994530-C-T is described in ClinVar as [Benign]. Clinvar id is 1294929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107984124	XR_007060857.1	n.127+5149G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000523884.1	n.149-9612G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16028 AN: 152008 Hom.: 966 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0910

GnomAD4 exome AF: 0.112 AC: 137627 AN: 1232650 Hom.: 8610 Cov.: 17 AF XY: 0.114 AC XY: 70309 AN XY: 616042

Gnomad4 AFR exome AF: 0.0749

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0999

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.106 AC: 16057 AN: 152126 Hom.: 974 Cov.: 32 AF XY: 0.109 AC XY: 8102 AN XY: 74352

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.104 Hom.: 200

Bravo AF: 0.102

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.1
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3739377; hg19: chr8-22852043;