Variant 5-73894487-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001177693.2(ARHGEF28):c.3753C>T(p.Asp1251Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,613,868 control chromosomes in the GnomAD database, including 1,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 114 hom., cov: 33)

Exomes 𝑓: 0.020 ( 1104 hom. )

Consequence

ARHGEF28
NM_001177693.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.231

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 5-73894487-C-T is Benign according to our data. Variant chr5-73894487-C-T is described in ClinVar as [Benign]. Clinvar id is 257369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73894487-C-T is described in Lovd as [Likely_benign]. Variant chr5-73894487-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.231 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0925 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.3753C>T	p.Asp1251Asp	synonymous_variant	29/36	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.3753C>T	p.Asp1251Asp	synonymous_variant	29/36	5	NM_001177693.2	ENSP00000441436.1		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3018

AN:

152148

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00657

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0961

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0384

AC:

9554

AN:

248892

Hom.:

776

AF XY:

0.0326

AC XY:

4406

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.00538

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0202

AC:

29485

AN:

1461602

Hom.:

1104

Cov.:

AF XY:

0.0195

AC XY:

14147

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00454

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.00116

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.00581

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0199

AC:

3029

AN:

152266

Hom.:

114

Cov.:

AF XY:

0.0201

AC XY:

1498

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00657

Gnomad4 AMR

AF:

0.0966

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0239

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.0143

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0155

Hom.:

Bravo

AF:

0.0283

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
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	-	- -

not specified

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.9

DANN

Benign

0.36

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