rs34896

Variant names:

• chr5-95748427-G-A
• rs34896
• NM_014899.4:c.510G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-95748427-G-A
• chr5-95748427-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014899.4(RHOBTB3):​c.510G>A​(p.Ala170Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,610,656 control chromosomes in the GnomAD database, including 148,986 homozygotes. 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: 𝑓 0.40 (12750 hom., cov: 32)
  • Exomes 𝑓: 0.43 (136236 hom.)
• Consequence: RHOBTB3 NM_014899.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00
• Publications: 34 publications found

Genes affected

RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014899.4. 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
	RHOBTB3	NM_014899.4	MANE Select	c.510G>A	p.Ala170Ala	synonymous	Exon 4 of 12	NP_055714.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOBTB3	ENST00000379982.8	TSL:1 MANE Select	c.510G>A	p.Ala170Ala	synonymous	Exon 4 of 12	ENSP00000369318.3	O94955
	RHOBTB3	ENST00000890088.1		c.507G>A	p.Ala169Ala	synonymous	Exon 4 of 11	ENSP00000560147.1
	RHOBTB3	ENST00000958070.1		c.510G>A	p.Ala170Ala	synonymous	Exon 4 of 11	ENSP00000628129.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60592 AN: 151956 Hom.: 12744 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.429

GnomAD2 exomes AF: 0.441 AC: 110790 AN: 251044 AF XY: 0.450

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.711

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.426 AC: 621440 AN: 1458582 Hom.: 136236 Cov.: 32 AF XY: 0.430 AC XY: 312405 AN XY: 725704

African (AFR) AF: 0.292 AC: 9750 AN: 33410

American (AMR) AF: 0.355 AC: 15862 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 12672 AN: 26072

East Asian (EAS) AF: 0.738 AC: 29265 AN: 39630

South Asian (SAS) AF: 0.518 AC: 44551 AN: 86010

European-Finnish (FIN) AF: 0.463 AC: 24688 AN: 53354

Middle Eastern (MID) AF: 0.428 AC: 2463 AN: 5756

European-Non Finnish (NFE) AF: 0.411 AC: 456286 AN: 1109432

Other (OTH) AF: 0.430 AC: 25903 AN: 60264

GnomAD4 genome AF: 0.399 AC: 60623 AN: 152074 Hom.: 12750 Cov.: 32 AF XY: 0.403 AC XY: 29926 AN XY: 74332

African (AFR) AF: 0.303 AC: 12582 AN: 41474

American (AMR) AF: 0.365 AC: 5572 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3472

East Asian (EAS) AF: 0.713 AC: 3694 AN: 5178

South Asian (SAS) AF: 0.530 AC: 2558 AN: 4822

European-Finnish (FIN) AF: 0.451 AC: 4774 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.416 AC: 28279 AN: 67956

Other (OTH) AF: 0.435 AC: 919 AN: 2112

Alfa AF: 0.413 Hom.: 54805

Bravo AF: 0.389

Asia WGS AF: 0.585 AC: 2035 AN: 3476

EpiCase AF: 0.422

EpiControl AF: 0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.69
DANN	Benign	0.48
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34896; hg19: chr5-95084131; COSMIC: COSV66102097; COSMIC: COSV66102097;