Variant 5-73795403-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001177693.2(ARHGEF28):c.1024+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,607,310 control chromosomes in the GnomAD database, including 167,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13146 hom., cov: 31)

Exomes 𝑓: 0.46 ( 154249 hom. )

Consequence

ARHGEF28
NM_001177693.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.86

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 5-73795403-C-T is Benign according to our data. Variant chr5-73795403-C-T is described in ClinVar as [Benign]. Clinvar id is 257357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73795403-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ARHGEF28	NM_001177693.2 linkuse as main transcript	c.1024+12C>T	intron_variant	ENST00000513042.7
ARHGEF28	NM_001080479.3 linkuse as main transcript	c.1024+12C>T	intron_variant
ARHGEF28	NM_001388076.1 linkuse as main transcript	c.730+12C>T	intron_variant
ARHGEF28	NM_001388078.1 linkuse as main transcript	c.1024+12C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF28	ENST00000513042.7 linkuse as main transcript	c.1024+12C>T		intron_variant		5	NM_001177693.2		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62068

AN:

151812

Hom.:

13137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.429

AC:

106721

AN:

248586

Hom.:

23452

AF XY:

0.430

AC XY:

57950

AN XY:

134840

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.277

Gnomad SAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.470

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.457

AC:

664962

AN:

1455378

Hom.:

154249

Cov.:

AF XY:

0.455

AC XY:

329559

AN XY:

724346

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.494

Gnomad4 NFE exome

AF:

0.476

Gnomad4 OTH exome

AF:

0.436

GnomAD4 genome

AF:

0.409

AC:

62102

AN:

151932

Hom.:

13146

Cov.:

AF XY:

0.408

AC XY:

30319

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.404

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.492

Gnomad4 NFE

AF:

0.467

Gnomad4 OTH

AF:

0.405

Alfa

AF:

0.431

Hom.:

8348

Bravo

AF:

0.399

Asia WGS

AF:

0.307

AC:

1069

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.13

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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