chr5-95748427-G-A

Position:

• chr5-95748427-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014899.4(RHOBTB3):​c.510G>A​(p.Ala170=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOBTB3	NM_014899.4	c.510G>A	p.Ala170=	synonymous_variant	4/12	ENST00000379982.8	NP_055714.3
RHOBTB3	XM_011543279.3	c.510G>A	p.Ala170=	synonymous_variant	4/11		XP_011541581.1
RHOBTB3	XM_017009237.2	c.-73G>A		5_prime_UTR_variant	4/12		XP_016864726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOBTB3	ENST00000379982.8	c.510G>A	p.Ala170=	synonymous_variant	4/12	1	NM_014899.4	ENSP00000369318	P1

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

GnomAD3 exomes AF: 0.441 AC: 110790 AN: 251044 Hom.: 25644 AF XY: 0.450 AC XY: 61003 AN XY: 135682

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 SAS exome AF: 0.517

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

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.486

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.430

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

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.435

Alfa AF: 0.414 Hom.: 25544

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.69
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

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