chr8-22994530-C-T

Variant names:

• chr8-22994530-C-T
• rs3739377
• ENST00000519685.5:c.-23-31C>T

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.-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 NM_001160036.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.180
• Publications: 5 publications found

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]

RHOBTB2-AS1 (HGNC:58239):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1294929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160036.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOBTB2	NM_001160036.2		c.-23-31C>T		intron	N/A	NP_001153508.1	Q9BYZ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOBTB2	ENST00000519685.5	TSL:1	c.-23-31C>T		intron	N/A	ENSP00000427926.1	Q9BYZ6-2
	RHOBTB2	ENST00000867414.1		c.-89-31C>T		intron	N/A	ENSP00000537473.1
	RHOBTB2	ENST00000867415.1		c.-719-31C>T		intron	N/A	ENSP00000537474.1

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

African (AFR) AF: 0.0749 AC: 2092 AN: 27942

American (AMR) AF: 0.128 AC: 4445 AN: 34818

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2928 AN: 24044

East Asian (EAS) AF: 0.224 AC: 7834 AN: 35010

South Asian (SAS) AF: 0.205 AC: 15515 AN: 75612

European-Finnish (FIN) AF: 0.111 AC: 5434 AN: 48968

Middle Eastern (MID) AF: 0.0778 AC: 418 AN: 5372

European-Non Finnish (NFE) AF: 0.0999 AC: 92757 AN: 928532

Other (OTH) AF: 0.119 AC: 6204 AN: 52352

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

African (AFR) AF: 0.0770 AC: 3197 AN: 41520

American (AMR) AF: 0.108 AC: 1656 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1119 AN: 5150

South Asian (SAS) AF: 0.221 AC: 1064 AN: 4816

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7101 AN: 67996

Other (OTH) AF: 0.0962 AC: 203 AN: 2110

Alfa AF: 0.104 Hom.: 1355

Bravo AF: 0.102

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.70
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3739377; hg19: chr8-22852043; COSMIC: COSV101581494; COSMIC: COSV101581494;