rs6948196

Positions:

• chr7-151516126-T-C

Variant summary

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

The NM_005614.4(RHEB):​c.52+3334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,948 control chromosomes in the GnomAD database, including 20,108 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 0.51 (20108 hom., cov: 31)
• Consequence: RHEB NM_005614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHEB	NM_005614.4	c.52+3334A>G		intron_variant		ENST00000262187.10	NP_005605.1
RHEB	XM_011516457.3	c.-74+3334A>G		intron_variant			XP_011514759.1
RHEB	XM_024446854.2	c.-74+2634A>G		intron_variant			XP_024302622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHEB	ENST00000262187.10	c.52+3334A>G		intron_variant		1	NM_005614.4	ENSP00000262187.5

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77836 AN: 151830 Hom.: 20076 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.513 AC: 77918 AN: 151948 Hom.: 20108 Cov.: 31 AF XY: 0.516 AC XY: 38325 AN XY: 74228

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.507

Alfa AF: 0.507 Hom.: 2472

Bravo AF: 0.510

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.23

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: rs6948196; hg19: chr7-151213212;