7-151487899-C-T

Variant names:

• chr7-151487899-C-T
• rs3753151
• NM_005614.4:c.124+3044G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005614.4(RHEB):​c.124+3044G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,006 control chromosomes in the GnomAD database, including 25,104 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 0.57 (25104 hom., cov: 32)
• Consequence: RHEB NM_005614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 6 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 = 0.629 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.124+3044G>A		intron	N/A	NP_005605.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHEB	ENST00000262187.10	TSL:1 MANE Select	c.124+3044G>A		intron	N/A	ENSP00000262187.5
	RHEB	ENST00000876654.1		c.124+3044G>A		intron	N/A	ENSP00000546713.1
	RHEB	ENST00000924902.1		c.124+3044G>A		intron	N/A	ENSP00000594961.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86874 AN: 151888 Hom.: 25065 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.572 AC: 86966 AN: 152006 Hom.: 25104 Cov.: 32 AF XY: 0.576 AC XY: 42780 AN XY: 74280

African (AFR) AF: 0.611 AC: 25343 AN: 41474

American (AMR) AF: 0.587 AC: 8974 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2289 AN: 3468

East Asian (EAS) AF: 0.517 AC: 2671 AN: 5168

South Asian (SAS) AF: 0.648 AC: 3118 AN: 4810

European-Finnish (FIN) AF: 0.534 AC: 5629 AN: 10548

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37242 AN: 67946

Other (OTH) AF: 0.570 AC: 1200 AN: 2104

Alfa AF: 0.562 Hom.: 77285

Bravo AF: 0.576

Asia WGS AF: 0.598 AC: 2080 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	1.7
DANN	Benign	0.76
PhyloP100		-0.40
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: rs3753151; hg19: chr7-151184985;