Variant rs2973568 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.1680A>G(p.Ser560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,575,968 control chromosomes in the GnomAD database, including 282,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35574 hom., cov: 32)

Exomes 𝑓: 0.59 ( 247057 hom. )

Consequence

ARHGEF28
NM_001177693.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.175

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 5-73849020-A-G is Benign according to our data. Variant chr5-73849020-A-G is described in ClinVar as [Benign]. Clinvar id is 257359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73849020-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.175 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 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.1680A>G	p.Ser560=	synonymous_variant	13/36	ENST00000513042.7	NP_001171164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7 linkuse as main transcript	c.1680A>G	p.Ser560=	synonymous_variant	13/36	5	NM_001177693.2	ENSP00000441436		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101220

AN:

151854

Hom.:

35507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.899

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.642

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.655

GnomAD3 exomes

AF:

0.596

AC:

119906

AN:

201102

Hom.:

36586

AF XY:

0.591

AC XY:

63305

AN XY:

107168

show subpopulations

Gnomad AFR exome

AF:

0.904

Gnomad AMR exome

AF:

0.639

Gnomad ASJ exome

AF:

0.584

Gnomad EAS exome

AF:

0.523

Gnomad SAS exome

AF:

0.613

Gnomad FIN exome

AF:

0.524

Gnomad NFE exome

AF:

0.563

Gnomad OTH exome

AF:

0.587

GnomAD4 exome

AF:

0.585

AC:

833504

AN:

1423994

Hom.:

247057

Cov.:

AF XY:

0.584

AC XY:

411654

AN XY:

704906

show subpopulations

Gnomad4 AFR exome

AF:

0.916

Gnomad4 AMR exome

AF:

0.637

Gnomad4 ASJ exome

AF:

0.576

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.613

Gnomad4 FIN exome

AF:

0.533

Gnomad4 NFE exome

AF:

0.577

Gnomad4 OTH exome

AF:

0.599

GnomAD4 genome

AF:

0.667

AC:

101348

AN:

151974

Hom.:

35574

Cov.:

AF XY:

0.662

AC XY:

49124

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.899

Gnomad4 AMR

AF:

0.643

Gnomad4 ASJ

AF:

0.578

Gnomad4 EAS

AF:

0.522

Gnomad4 SAS

AF:

0.624

Gnomad4 FIN

AF:

0.522

Gnomad4 NFE

AF:

0.571

Gnomad4 OTH

AF:

0.657

Alfa

AF:

0.593

Hom.:

32921

Bravo

AF:

0.689

Asia WGS

AF:

0.622

AC:

2159

AN:

3476

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, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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

-0.47

CADD

Benign

7.1

DANN

Benign

0.64

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