Variant 5-73753050-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001177693.2(ARHGEF28):c.323A>G(p.Asn108Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,610,548 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 14 hom. )

Consequence

ARHGEF28
NM_001177693.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034273565).

BP6

Variant 5-73753050-A-G is Benign according to our data. Variant chr5-73753050-A-G is described in ClinVar as [Benign]. Clinvar id is 809767.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARHGEF28	NM_001177693.2 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	4/36	ENST00000513042.7	NP_001171164.1
ARHGEF28	NM_001080479.3 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	4/37		NP_001073948.2
ARHGEF28	NM_001388078.1 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	4/35		NP_001375007.1
ARHGEF28	NM_001388076.1 linkuse as main transcript	c.181+3066A>G		intron_variant			NP_001375005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	4/36	5	NM_001177693.2	ENSP00000441436		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

457

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00362

AC:

875

AN:

241440

Hom.:

AF XY:

0.00399

AC XY:

523

AN XY:

131092

show subpopulations

Gnomad AFR exome

AF:

0.000684

Gnomad AMR exome

AF:

0.00262

Gnomad ASJ exome

AF:

0.000918

Gnomad EAS exome

AF:

0.0000568

Gnomad SAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00357

GnomAD4 exome

AF:

0.00342

AC:

4993

AN:

1458248

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

2527

AN XY:

725060

show subpopulations

Gnomad4 AFR exome

AF:

0.000599

Gnomad4 AMR exome

AF:

0.00272

Gnomad4 ASJ exome

AF:

0.000962

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00586

Gnomad4 FIN exome

AF:

0.00930

Gnomad4 NFE exome

AF:

0.00326

Gnomad4 OTH exome

AF:

0.00322

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152300

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00326

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00229

ESP6500AA

AF:

0.00139

AC:

ESP6500EA

AF:

0.00387

AC:

ExAC

AF:

0.00339

AC:

411

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

ARHGEF28: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0042

.;.;T;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.76

T;T;T;.;.

MetaRNN

Benign

0.0034

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.23

N;N;N;N;N

REVEL

Benign

0.038

Sift

Benign

0.15

T;T;T;T;T

Sift4G

Benign

0.36

T;T;T;T;T

Polyphen

0.044

B;.;B;.;B

Vest4

0.057

MVP

0.16

MPC

0.058

ClinPred

0.0057

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.17

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