rs875588

Positions:

• chr7-151471744-C-T

Variant summary

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

The NM_005614.4(RHEB):​c.276-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 614,338 control chromosomes in the GnomAD database, including 81,380 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 0.52 (20948 hom., cov: 33)
  • Exomes 𝑓: 0.51 (60432 hom.)
• Consequence: RHEB NM_005614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

Genes affected

RHEB (HGNC:10011): (Ras homolog, mTORC1 binding) This gene is a member of the small GTPase superfamily and encodes a lipid-anchored, cell membrane protein with five repeats of the RAS-related GTP-binding region. This protein is vital in regulation of growth and cell cycle progression due to its role in the insulin/TOR/S6K signaling pathway. The protein has GTPase activity and shuttles between a GDP-bound form and a GTP-bound form, and farnesylation of the protein is required for this activity. Three pseudogenes have been mapped, two on chromosome 10 and one on chromosome 22. [provided by RefSeq, Jul 2008]

RHEB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHEB	NM_005614.4	c.276-139G>A		intron_variant		ENST00000262187.10	NP_005605.1
RHEB	XM_011516457.3	c.243-139G>A		intron_variant			XP_011514759.1
RHEB	XM_024446854.2	c.243-139G>A		intron_variant			XP_024302622.1
RHEB	XM_047420685.1	c.243-139G>A		intron_variant			XP_047276641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHEB	ENST00000262187.10	c.276-139G>A		intron_variant		1	NM_005614.4	ENSP00000262187.5

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79511 AN: 151950 Hom.: 20916 Cov.: 33

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.507 AC: 234564 AN: 462270 Hom.: 60432 Cov.: 5 AF XY: 0.512 AC XY: 124651 AN XY: 243622

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.510

GnomAD4 genome AF: 0.523 AC: 79596 AN: 152068 Hom.: 20948 Cov.: 33 AF XY: 0.526 AC XY: 39096 AN XY: 74342

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.512

Alfa AF: 0.513 Hom.: 3582

Bravo AF: 0.521

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.50

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: rs875588; hg19: chr7-151168830;