5-73794436-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001177693.2(ARHGEF28):c.945T>C(p.Ala315Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,599,254 control chromosomes in the GnomAD database, including 235,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28349 hom., cov: 30)

Exomes 𝑓: 0.53 ( 206851 hom. )

Consequence

ARHGEF28
NM_001177693.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.71

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD, AR Classification: MODERATE Submitted by: Genomics England PanelApp

ARHGEF28 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-73794436-T-C is Benign according to our data. Variant chr5-73794436-T-C is described in ClinVar as Benign. ClinVar VariationId is 257379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ARHGEF28	NM_001177693.2 link	c.945T>C	p.Ala315Ala	synonymous_variant	Exon 8 of 36	ENST00000513042.7	NP_001171164.1
ARHGEF28	NM_001080479.3 link	c.945T>C	p.Ala315Ala	synonymous_variant	Exon 8 of 37		NP_001073948.2
ARHGEF28	NM_001388078.1 link	c.945T>C	p.Ala315Ala	synonymous_variant	Exon 8 of 35		NP_001375007.1
ARHGEF28	NM_001388076.1 link	c.651T>C	p.Ala217Ala	synonymous_variant	Exon 7 of 35		NP_001375005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7 link	c.945T>C	p.Ala315Ala	synonymous_variant	Exon 8 of 36	5	NM_001177693.2	ENSP00000441436.1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90764

AN:

151696

Hom.:

28302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.563

GnomAD2 exomes

AF:

0.551

AC:

128889

AN:

233804

AF XY:

0.543

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.593

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.537

Gnomad FIN exome

AF:

0.550

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.521

GnomAD4 exome

AF:

0.532

AC:

770203

AN:

1447438

Hom.:

206851

Cov.:

AF XY:

0.531

AC XY:

381695

AN XY:

719020

show subpopulations

African (AFR)

AF:

0.794

AC:

26354

AN:

33178

American (AMR)

AF:

0.584

AC:

25291

AN:

43320

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

11336

AN:

25884

East Asian (EAS)

AF:

0.485

AC:

19109

AN:

39418

South Asian (SAS)

AF:

0.554

AC:

46424

AN:

83848

European-Finnish (FIN)

AF:

0.549

AC:

29069

AN:

52920

Middle Eastern (MID)

AF:

0.495

AC:

2849

AN:

5760

European-Non Finnish (NFE)

AF:

0.524

AC:

577590

AN:

1103162

Other (OTH)

AF:

0.537

AC:

32181

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15869

31738

47607

63476

79345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16792

33584

50376

67168

83960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.599

AC:

90867

AN:

151816

Hom.:

28349

Cov.:

AF XY:

0.598

AC XY:

44371

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.791

AC:

32755

AN:

41408

American (AMR)

AF:

0.558

AC:

8518

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1516

AN:

3468

East Asian (EAS)

AF:

0.520

AC:

2677

AN:

5150

South Asian (SAS)

AF:

0.565

AC:

2716

AN:

4806

European-Finnish (FIN)

AF:

0.550

AC:

5775

AN:

10506

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35037

AN:

67908

Other (OTH)

AF:

0.566

AC:

1195

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1763

3526

5289

7052

8815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.542

Hom.:

94069

Bravo

AF:

0.609

Asia WGS

AF:

0.571

AC:

1986

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.044

(source)

DANN

Benign

0.26

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over