rs6948196

Variant names:

• chr7-151516126-T-C
• rs6948196
• NM_005614.4:c.52+3334A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005614.4. 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
	RHEB	NM_005614.4	MANE Select	c.52+3334A>G		intron	N/A	NP_005605.1	A0A090N900

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHEB	ENST00000262187.10	TSL:1 MANE Select	c.52+3334A>G		intron	N/A	ENSP00000262187.5	Q15382
	RHEB	ENST00000876654.1		c.52+3334A>G		intron	N/A	ENSP00000546713.1
	RHEB	ENST00000924902.1		c.52+3334A>G		intron	N/A	ENSP00000594961.1

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

African (AFR) AF: 0.528 AC: 21882 AN: 41446

American (AMR) AF: 0.492 AC: 7499 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2132 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2204 AN: 5172

South Asian (SAS) AF: 0.601 AC: 2893 AN: 4816

European-Finnish (FIN) AF: 0.488 AC: 5137 AN: 10524

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34627 AN: 67962

Other (OTH) AF: 0.507 AC: 1070 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.23
PhyloP100		-0.28
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: rs6948196; hg19: chr7-151213212;