Variant rs2931423 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001177693.2(ARHGEF28):c.2283C>T(p.Gly761Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,613,324 control chromosomes in the GnomAD database, including 81,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6591 hom., cov: 32)

Exomes 𝑓: 0.31 ( 74569 hom. )

Consequence

ARHGEF28
NM_001177693.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.464

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 -16 ACMG points.

BP6

Variant 5-73868006-C-T is Benign according to our data. Variant chr5-73868006-C-T is described in ClinVar as [Benign]. Clinvar id is 257362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73868006-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 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.2283C>T	p.Gly761Gly	synonymous_variant	19/36	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.2283C>T	p.Gly761Gly	synonymous_variant	19/36	5	NM_001177693.2	ENSP00000441436.1		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43370

AN:

151924

Hom.:

6582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.285

GnomAD3 exomes

AF:

0.301

AC:

74801

AN:

248468

Hom.:

12290

AF XY:

0.292

AC XY:

39392

AN XY:

134784

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.463

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.315

AC:

459673

AN:

1461282

Hom.:

74569

Cov.:

AF XY:

0.310

AC XY:

225364

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.451

Gnomad4 ASJ exome

AF:

0.295

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.285

AC:

43408

AN:

152042

Hom.:

6591

Cov.:

AF XY:

0.281

AC XY:

20850

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.324

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.313

Hom.:

15184

Bravo

AF:

0.292

Asia WGS

AF:

0.156

AC:

544

AN:

3476

EpiCase

AF:

0.315

EpiControl

AF:

0.312

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.52

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.52

Position offset: -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