8-22995709-C-G

Variant names:

• chr8-22995709-C-G
• rs112400641
• ENST00000519685.5:c.56+1070C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001160036.2(RHOBTB2):​c.56+1070C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00577 in 747,402 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (91 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (45 hom.)
• Consequence: RHOBTB2 NM_001160036.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 8-22995709-C-G is Benign according to our data. Variant chr8-22995709-C-G is described in ClinVar as [Benign]. Clinvar id is 1243399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOBTB2	NM_001160036.2	c.56+1070C>G		intron_variant	Intron 3 of 11		NP_001153508.1
RHOBTB2	XM_047421607.1	c.56+1070C>G		intron_variant	Intron 3 of 11		XP_047277563.1
RHOBTB2	XM_047421608.1	c.56+1070C>G		intron_variant	Intron 3 of 11		XP_047277564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOBTB2	ENST00000519685.5	c.56+1070C>G		intron_variant	Intron 3 of 11	1		ENSP00000427926.1
RHOBTB2	ENST00000524077.5	c.56+1070C>G		intron_variant	Intron 3 of 5	3		ENSP00000430785.1
PEBP4	ENST00000522278.1	c.144+3970G>C		intron_variant	Intron 1 of 1	5		ENSP00000429414.1

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2899 AN: 152174 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00237 AC: 1411 AN: 595110 Hom.: 45 AF XY: 0.00196 AC XY: 615 AN XY: 313456

Gnomad4 AFR exome AF: 0.0673 AC: 1063 AN: 15806

Gnomad4 AMR exome AF: 0.00466 AC: 132 AN: 28354

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 16716

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 31842

Gnomad4 SAS exome AF: 0.000109 AC: 6 AN: 55276

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 44770

Gnomad4 NFE exome AF: 0.000147 AC: 54 AN: 368538

Gnomad4 Remaining exome AF: 0.00497 AC: 153 AN: 30790

GnomAD4 genome AF: 0.0190 AC: 2899 AN: 152292 Hom.: 91 Cov.: 32 AF XY: 0.0179 AC XY: 1333 AN XY: 74452

Gnomad4 AFR AF: 0.0651 AC: 0.0651054 AN: 0.0651054

Gnomad4 AMR AF: 0.00856 AC: 0.00856209 AN: 0.00856209

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207125 AN: 0.000207125

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000294 AC: 0.000294023 AN: 0.000294023

Gnomad4 OTH AF: 0.0198 AC: 0.0198488 AN: 0.0198488

Alfa AF: 0.0146 Hom.: 6

Bravo AF: 0.0226

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.6
DANN	Benign	0.82
Mutation Taster		=100/0	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112400641; hg19: chr8-22853222;