rs1897367

Positions:

• chr10-60906635-A-G
• chr10-60906635-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014836.5(RHOBTB1):​c.296+4252T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,966 control chromosomes in the GnomAD database, including 6,612 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 0.25 (6612 hom., cov: 32)
• Consequence: RHOBTB1 NM_014836.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

Genes affected

RHOBTB1 (HGNC:18738): (Rho related BTB domain containing 1) The protein encoded by this gene belongs to the Rho family of the small GTPase superfamily. It contains a GTPase domain, a proline-rich region, a tandem of 2 BTB (broad complex, tramtrack, and bric-a-brac) domains, and a conserved C-terminal region. The protein plays a role in small GTPase-mediated signal transduction and the organization of the actin filament system. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOBTB1	NM_014836.5	c.296+4252T>C		intron_variant		ENST00000337910.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOBTB1	ENST00000337910.10	c.296+4252T>C		intron_variant		1	NM_014836.5	P1
RHOBTB1	ENST00000357917.4	c.296+4252T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38491 AN: 151848 Hom.: 6588 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38556 AN: 151966 Hom.: 6612 Cov.: 32 AF XY: 0.255 AC XY: 18935 AN XY: 74278

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.216

Alfa AF: 0.144 Hom.: 613

Bravo AF: 0.263

Asia WGS AF: 0.238 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.49

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: rs1897367; hg19: chr10-62666393;