7-151495576-C-T

Variant names:

• chr7-151495576-C-T
• rs2299965
• NM_005614.4:c.53-4562G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005614.4(RHEB):​c.53-4562G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,988 control chromosomes in the GnomAD database, including 17,740 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 0.48 (17740 hom., cov: 32)
• Consequence: RHEB NM_005614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHEB	NM_005614.4	c.53-4562G>A		intron_variant	Intron 1 of 7	ENST00000262187.10	NP_005605.1
RHEB	XM_011516457.3	c.19+2513G>A		intron_variant	Intron 2 of 8		XP_011514759.1
RHEB	XM_024446854.2	c.19+2513G>A		intron_variant	Intron 2 of 8		XP_024302622.1
RHEB	XM_047420685.1	c.19+2513G>A		intron_variant	Intron 2 of 8		XP_047276641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHEB	ENST00000262187.10	c.53-4562G>A		intron_variant	Intron 1 of 7	1	NM_005614.4	ENSP00000262187.5

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72822 AN: 151870 Hom.: 17718 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.480 AC: 72892 AN: 151988 Hom.: 17740 Cov.: 32 AF XY: 0.484 AC XY: 35955 AN XY: 74300

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.485

Alfa AF: 0.486 Hom.: 7592

Bravo AF: 0.472

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.040
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs2299965; hg19: chr7-151192662;