chr7-151471744-C-T

Variant names:

• chr7-151471744-C-T
• rs875588
• NM_005614.4:c.276-139G>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.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
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 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.276-139G>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.276-139G>A		intron	N/A	ENSP00000262187.5
	RHEB	ENST00000876654.1		c.276-303G>A		intron	N/A	ENSP00000546713.1
	RHEB	ENST00000924902.1		c.276-1092G>A		intron	N/A	ENSP00000594961.1

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

African (AFR) AF: 0.568 AC: 6752 AN: 11892

American (AMR) AF: 0.432 AC: 6433 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 8404 AN: 13666

East Asian (EAS) AF: 0.424 AC: 12800 AN: 30174

South Asian (SAS) AF: 0.581 AC: 22477 AN: 38714

European-Finnish (FIN) AF: 0.488 AC: 21712 AN: 44454

Middle Eastern (MID) AF: 0.511 AC: 1024 AN: 2004

European-Non Finnish (NFE) AF: 0.505 AC: 141726 AN: 280534

Other (OTH) AF: 0.510 AC: 13236 AN: 25932

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

African (AFR) AF: 0.568 AC: 23574 AN: 41468

American (AMR) AF: 0.492 AC: 7519 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2205 AN: 5172

South Asian (SAS) AF: 0.598 AC: 2881 AN: 4820

European-Finnish (FIN) AF: 0.486 AC: 5143 AN: 10580

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34584 AN: 67964

Other (OTH) AF: 0.512 AC: 1083 AN: 2114

Alfa AF: 0.514 Hom.: 3714

Bravo AF: 0.521

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		0.22
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: rs875588; hg19: chr7-151168830;