7-151472933-C-T

Variant names:

• chr7-151472933-C-T
• rs1109089
• NM_005614.4:c.276-1328G>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.276-1328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,122 control chromosomes in the GnomAD database, including 14,128 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 0.40 (14128 hom., cov: 33)
• Consequence: RHEB NM_005614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 9 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 = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHEB	NM_005614.4	c.276-1328G>A		intron_variant	Intron 4 of 7	ENST00000262187.10	NP_005605.1
RHEB	XM_011516457.3	c.243-1328G>A		intron_variant	Intron 5 of 8		XP_011514759.1
RHEB	XM_024446854.2	c.243-1328G>A		intron_variant	Intron 5 of 8		XP_024302622.1
RHEB	XM_047420685.1	c.243-1328G>A		intron_variant	Intron 5 of 8		XP_047276641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHEB	ENST00000262187.10	c.276-1328G>A		intron_variant	Intron 4 of 7	1	NM_005614.4	ENSP00000262187.5

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60530 AN: 152004 Hom.: 14121 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.398 AC: 60541 AN: 152122 Hom.: 14128 Cov.: 33 AF XY: 0.404 AC XY: 30025 AN XY: 74360

African (AFR) AF: 0.139 AC: 5760 AN: 41508

American (AMR) AF: 0.438 AC: 6696 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2202 AN: 5174

South Asian (SAS) AF: 0.595 AC: 2870 AN: 4820

European-Finnish (FIN) AF: 0.486 AC: 5133 AN: 10564

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.507 AC: 34445 AN: 67994

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.437 Hom.: 2016

Bravo AF: 0.377

Asia WGS AF: 0.480 AC: 1666 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	0.45
DANN	Benign	0.57
PhyloP100		-0.97
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: rs1109089; hg19: chr7-151170019;