7-151474576-G-T

Variant names:

• chr7-151474576-G-T
• rs6972955
• NM_005614.4:c.275+2757C>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.275+2757C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,974 control chromosomes in the GnomAD database, including 15,289 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 0.45 (15289 hom., cov: 32)
• Consequence: RHEB NM_005614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 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.275+2757C>A		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.275+2757C>A		intron	N/A	ENSP00000262187.5	Q15382
	RHEB	ENST00000876654.1		c.275+2757C>A		intron	N/A	ENSP00000546713.1
	RHEB	ENST00000924902.1		c.275+2757C>A		intron	N/A	ENSP00000594961.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68019 AN: 151856 Hom.: 15277 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.448 AC: 68075 AN: 151974 Hom.: 15289 Cov.: 32 AF XY: 0.451 AC XY: 33528 AN XY: 74284

African (AFR) AF: 0.410 AC: 16997 AN: 41410

American (AMR) AF: 0.466 AC: 7116 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2027 AN: 3466

East Asian (EAS) AF: 0.525 AC: 2720 AN: 5184

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4445 AN: 10528

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30831 AN: 67972

Other (OTH) AF: 0.437 AC: 923 AN: 2110

Alfa AF: 0.450 Hom.: 47793

Bravo AF: 0.445

Asia WGS AF: 0.519 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.53
PhyloP100		-0.052
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6972955; hg19: chr7-151171662;