Variant 12-49069767-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000301068.11(RHEBL1):c.19A>G(p.Arg7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RHEBL1
ENST00000301068.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.482

Variant links:

Genes affected

RHEBL1 (HGNC:21166): (RHEB like 1) Enables GTP binding activity. Involved in TOR signaling and positive regulation of NF-kappaB transcription factor activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RHEBL1 links:

RHEBL1 (HGNC:):

RHEBL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHEBL1	NM_144593.3 linkuse as main transcript	c.19A>G	p.Arg7Gly	missense_variant	1/8	ENST00000301068.11	NP_653194.1	Q8TAI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHEBL1	ENST00000301068.11 linkuse as main transcript	c.19A>G	p.Arg7Gly	missense_variant	1/8	1	NM_144593.3	ENSP00000301068.6	Q8TAI7-1
RHEBL1	ENST00000420065.5 linkuse as main transcript	n.19A>G		non_coding_transcript_exon_variant	1/7	1		ENSP00000409818.1	C9JQQ1
RHEBL1	ENST00000550797.1 linkuse as main transcript	n.19A>G		non_coding_transcript_exon_variant	1/8	1		ENSP00000446726.1	Q8TAI7-2
RHEBL1	ENST00000550675.1 linkuse as main transcript	c.19A>G	p.Arg7Gly	missense_variant	1/5	5		ENSP00000447428.1	F8W1T5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.19A>G (p.R7G) alteration is located in exon 1 (coding exon 1) of the RHEBL1 gene. This alteration results from a A to G substitution at nucleotide position 19, causing the arginine (R) at amino acid position 7 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.3

D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0070

D;.

Polyphen

0.97

D;.

Vest4

0.68

MutPred

0.68

Loss of methylation at R7 (P = 0.0405);Loss of methylation at R7 (P = 0.0405);

MVP

0.79

MPC

0.56

ClinPred

0.95

GERP RS

3.1

Varity_R

0.82

gMVP

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over