Variant 22-23693783-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153615.2(RGL4):c.721C>T(p.His241Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,613,264 control chromosomes in the GnomAD database, including 418,933 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.77 ( 46287 hom., cov: 31)

Exomes 𝑓: 0.71 ( 372646 hom. )

Consequence

RGL4
NM_153615.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

RGL4 (HGNC:31911): (ral guanine nucleotide dissociation stimulator like 4) This oncogene encodes a protein similar to guanine nucleotide exchange factor Ral guanine dissociation stimulator. Increased expression of this gene leads to translocation of the encoded protein to the cell membrane. The encoded protein can activate several pathways, including the Ras-Raf-MEK-ERK cascade. [provided by RefSeq, Jul 2016]

RGL4 links:

RGL4 (HGNC:):

RGL4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.5518795E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGL4	NM_153615.2 linkuse as main transcript	c.721C>T	p.His241Tyr	missense_variant	4/11	ENST00000290691.10	NP_705843.1	Q8IZJ4-1
RGL4	NM_001329424.3 linkuse as main transcript	c.721C>T	p.His241Tyr	missense_variant	4/12		NP_001316353.1	Q8IZJ4Q3ZCN2
GUSBP11	NR_024448.2 linkuse as main transcript	n.2561+336G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGL4	ENST00000290691.10 linkuse as main transcript	c.721C>T	p.His241Tyr	missense_variant	4/11	1	NM_153615.2	ENSP00000290691.5		Q8IZJ4-1
RGL4	ENST00000441897.5 linkuse as main transcript	n.721C>T		non_coding_transcript_exon_variant	6/14	2		ENSP00000396252.1		E9PH21

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117574

AN:

151928

Hom.:

46234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.925

Gnomad AMI

AF:

0.639

Gnomad AMR

AF:

0.781

Gnomad ASJ

AF:

0.794

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.702

Gnomad OTH

AF:

0.768

GnomAD3 exomes

AF:

0.729

AC:

183087

AN:

251264

Hom.:

67205

AF XY:

0.724

AC XY:

98383

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.928

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.787

Gnomad EAS exome

AF:

0.665

Gnomad SAS exome

AF:

0.731

Gnomad FIN exome

AF:

0.699

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.724

GnomAD4 exome

AF:

0.713

AC:

1041358

AN:

1461218

Hom.:

372646

Cov.:

AF XY:

0.713

AC XY:

518539

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.933

Gnomad4 AMR exome

AF:

0.770

Gnomad4 ASJ exome

AF:

0.788

Gnomad4 EAS exome

AF:

0.660

Gnomad4 SAS exome

AF:

0.732

Gnomad4 FIN exome

AF:

0.691

Gnomad4 NFE exome

AF:

0.702

Gnomad4 OTH exome

AF:

0.731

GnomAD4 genome

AF:

0.774

AC:

117687

AN:

152046

Hom.:

46287

Cov.:

AF XY:

0.774

AC XY:

57486

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.925

Gnomad4 AMR

AF:

0.781

Gnomad4 ASJ

AF:

0.794

Gnomad4 EAS

AF:

0.668

Gnomad4 SAS

AF:

0.735

Gnomad4 FIN

AF:

0.704

Gnomad4 NFE

AF:

0.702

Gnomad4 OTH

AF:

0.768

Alfa

AF:

0.718

Hom.:

80023

Bravo

AF:

0.784

TwinsUK

AF:

0.697

AC:

2585

ALSPAC

AF:

0.707

AC:

2726

ESP6500AA

AF:

0.926

AC:

4080

ESP6500EA

AF:

0.706

AC:

6073

ExAC

AF:

0.729

AC:

88449

Asia WGS

AF:

0.693

AC:

2412

AN:

3478

EpiCase

AF:

0.711

EpiControl

AF:

0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.16

DANN

Benign

0.57

DEOGEN2

Benign

0.020

.;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.51

T;T;T;T;T

MetaRNN

Benign

7.6e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.89

.;.;.;N;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

2.4

N;.;.;N;N

REVEL

Benign

0.072

Sift

Benign

1.0

T;.;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;.;.;B;.

Vest4

0.074

MPC

0.086

ClinPred

0.0034

GERP RS

-1.1

Varity_R

0.022

gMVP

0.19

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over