Variant 5-73753107-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001177693.2(ARHGEF28):c.380G>C(p.Gly127Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,595,062 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

ARHGEF28
NM_001177693.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.867

Variant links:

Genes affected

ARHGEF28 (HGNC:30322): (Rho guanine nucleotide exchange factor 28) This gene encodes a member of the Rho guanine nucleotide exchange factor family. The encoded protein interacts with low molecular weight neurofilament mRNA and may be involved in the formation of amyotrophic lateral sclerosis neurofilament aggregates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

ARHGEF28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069314837).

BP6

Variant 5-73753107-G-C is Benign according to our data. Variant chr5-73753107-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3037973.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARHGEF28	NM_001177693.2 linkuse as main transcript	c.380G>C	p.Gly127Ala	missense_variant	4/36	ENST00000513042.7
ARHGEF28	NM_001080479.3 linkuse as main transcript	c.380G>C	p.Gly127Ala	missense_variant	4/37
ARHGEF28	NM_001388078.1 linkuse as main transcript	c.380G>C	p.Gly127Ala	missense_variant	4/35
ARHGEF28	NM_001388076.1 linkuse as main transcript	c.181+3123G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF28	ENST00000513042.7 linkuse as main transcript	c.380G>C	p.Gly127Ala	missense_variant	4/36	5	NM_001177693.2		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

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

GnomAD3 exomes

AF:

0.000328

AC:

AN:

228386

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

122568

show subpopulations

Gnomad AFR exome

AF:

0.00319

Gnomad AMR exome

AF:

0.000731

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.0000970

AC:

140

AN:

1442744

Hom.:

Cov.:

AF XY:

0.0000978

AC XY:

AN XY:

715582

show subpopulations

Gnomad4 AFR exome

AF:

0.00303

Gnomad4 AMR exome

AF:

0.000623

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:

0.00000363

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152318

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00284

Gnomad4 AMR

AF:

0.00314

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

Alfa

AF:

0.000120

Hom.:

Bravo

AF:

0.000994

ESP6500AA

AF:

0.00209

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000322

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARHGEF28-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

Cadd

Benign

6.0

Dann

Benign

0.58

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.68

T;T;T;.;.

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0069

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

L;L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.050

N;N;N;N;N

REVEL

Benign

0.012

Sift

Benign

0.32

T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.17

B;.;B;.;B

Vest4

0.25

MVP

0.030

MPC

0.075

ClinPred

0.012

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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