Variant rs17552682 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001177693.2(ARHGEF28):c.267G>A(p.Val89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,613,496 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 13 hom., cov: 32)

Exomes 𝑓: 0.012 ( 164 hom. )

Consequence

ARHGEF28
NM_001177693.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.16

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=-0.42).

BP6

Variant 5-73752994-G-A is Benign according to our data. Variant chr5-73752994-G-A is described in ClinVar as [Benign]. Clinvar id is 257365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73752994-G-A is described in Lovd as [Benign]. Variant chr5-73752994-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00877 (1336/152334) while in subpopulation SAS AF= 0.0195 (94/4822). AF 95% confidence interval is 0.0163. There are 13 homozygotes in gnomad4. There are 643 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARHGEF28	NM_001177693.2 linkuse as main transcript	c.267G>A	p.Val89=	synonymous_variant	4/36	ENST00000513042.7	NP_001171164.1
ARHGEF28	NM_001080479.3 linkuse as main transcript	c.267G>A	p.Val89=	synonymous_variant	4/37		NP_001073948.2
ARHGEF28	NM_001388078.1 linkuse as main transcript	c.267G>A	p.Val89=	synonymous_variant	4/35		NP_001375007.1
ARHGEF28	NM_001388076.1 linkuse as main transcript	c.181+3010G>A		intron_variant			NP_001375005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7 linkuse as main transcript	c.267G>A	p.Val89=	synonymous_variant	4/36	5	NM_001177693.2	ENSP00000441436		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1334

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0108

AC:

2665

AN:

247902

Hom.:

AF XY:

0.0118

AC XY:

1583

AN XY:

134464

show subpopulations

Gnomad AFR exome

AF:

0.00176

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.0334

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0216

Gnomad FIN exome

AF:

0.00172

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.0118

AC:

17245

AN:

1461162

Hom.:

164

Cov.:

AF XY:

0.0123

AC XY:

8953

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00466

Gnomad4 ASJ exome

AF:

0.0352

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0199

Gnomad4 FIN exome

AF:

0.00176

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.00877

AC:

1336

AN:

152334

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

643

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.00900

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:2

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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