Variant 12-49069064-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000301068.11(RHEBL1):c.95C>T(p.Ser32Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RHEBL1
ENST00000301068.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.58

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12567994).

BP6

Variant 12-49069064-G-A is Benign according to our data. Variant chr12-49069064-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3314205.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHEBL1	NM_144593.3 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	2/8	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.95C>T	p.Ser32Leu	missense_variant	2/8	1	NM_144593.3	ENSP00000301068.6	Q8TAI7-1
RHEBL1	ENST00000420065.5 linkuse as main transcript	n.95C>T		non_coding_transcript_exon_variant	2/7	1		ENSP00000409818.1	C9JQQ1
RHEBL1	ENST00000550797.1 linkuse as main transcript	n.163C>T		non_coding_transcript_exon_variant	2/8	1		ENSP00000446726.1	Q8TAI7-2
RHEBL1	ENST00000550675.1 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	2/5	5		ENSP00000447428.1	F8W1T5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251400

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.049

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

3.1

N;N

REVEL

Benign

0.19

Sift

Benign

0.17

T;T

Sift4G

Benign

0.11

T;.

Polyphen

0.0

B;B

Vest4

0.099

MutPred

0.53

Loss of disorder (P = 0.0039);Loss of disorder (P = 0.0039);

MVP

0.55

MPC

0.37

ClinPred

0.32

GERP RS

3.0

Varity_R

0.093

gMVP

0.21

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