Variant rs61734875 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001177693.2(ARHGEF28):c.3294T>C(p.Ala1098Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 1,612,504 control chromosomes in the GnomAD database, including 2,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 174 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1882 hom. )

Consequence

ARHGEF28
NM_001177693.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.76

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:

ARHGEF28 (HGNC:):

ARHGEF28 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 5-73886088-T-C is Benign according to our data. Variant chr5-73886088-T-C is described in ClinVar as [Benign]. Clinvar id is 257368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73886088-T-C is described in Lovd as [Benign]. Variant chr5-73886088-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF28	NM_001177693.2 linkuse as main transcript	c.3294T>C	p.Ala1098Ala	synonymous_variant	25/36	ENST00000513042.7	NP_001171164.1	Q8N1W1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7 linkuse as main transcript	c.3294T>C	p.Ala1098Ala	synonymous_variant	25/36	5	NM_001177693.2	ENSP00000441436.1		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.0365

AC:

5558

AN:

152186

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00837

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0521

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0389

AC:

9642

AN:

248030

Hom.:

265

AF XY:

0.0392

AC XY:

5266

AN XY:

134496

show subpopulations

Gnomad AFR exome

AF:

0.00717

Gnomad AMR exome

AF:

0.0214

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.0513

Gnomad NFE exome

AF:

0.0522

Gnomad OTH exome

AF:

0.0434

GnomAD4 exome

AF:

0.0474

AC:

69269

AN:

1460200

Hom.:

1882

Cov.:

AF XY:

0.0464

AC XY:

33708

AN XY:

726202

show subpopulations

Gnomad4 AFR exome

AF:

0.00782

Gnomad4 AMR exome

AF:

0.0225

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.0515

Gnomad4 NFE exome

AF:

0.0525

Gnomad4 OTH exome

AF:

0.0450

GnomAD4 genome

AF:

0.0365

AC:

5557

AN:

152304

Hom.:

174

Cov.:

AF XY:

0.0362

AC XY:

2693

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00834

Gnomad4 AMR

AF:

0.0330

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0521

Gnomad4 NFE

AF:

0.0524

Gnomad4 OTH

AF:

0.0421

Alfa

AF:

0.0497

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0524

EpiControl

AF:

0.0542

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Apr 18, 2016	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.68

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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