Variant rs3749645 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.3018C>T(p.Tyr1006=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,569,962 control chromosomes in the GnomAD database, including 13,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1560 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12267 hom. )

Consequence

ARHGEF28
NM_001177693.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.25

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 5-73883847-C-T is Benign according to our data. Variant chr5-73883847-C-T is described in ClinVar as [Benign]. Clinvar id is 257366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73883847-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 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.3018C>T	p.Tyr1006=	synonymous_variant	24/36	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.3018C>T	p.Tyr1006=	synonymous_variant	24/36	5	NM_001177693.2	ENSP00000441436		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20591

AN:

151828

Hom.:

1560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.0896

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.128

AC:

24278

AN:

189534

Hom.:

1811

AF XY:

0.130

AC XY:

13131

AN XY:

100804

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0787

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.126

AC:

178372

AN:

1418016

Hom.:

12267

Cov.:

AF XY:

0.126

AC XY:

88612

AN XY:

701144

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0793

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.284

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.136

AC:

20602

AN:

151946

Hom.:

1560

Cov.:

AF XY:

0.136

AC XY:

10080

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.0893

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.288

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.121

Hom.:

2312

Bravo

AF:

0.137

Asia WGS

AF:

0.214

AC:

743

AN:

3478

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

-0.34

CADD

Benign

7.9

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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