5-73794436-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).

BP6

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

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	UniProt
ARHGEF28	NM_001177693.2 link	c.945T>C	p.Ala315Ala	synonymous_variant	Exon 8 of 36	ENST00000513042.7	NP_001171164.1	Q8N1W1-1
ARHGEF28	NM_001080479.3 link	c.945T>C	p.Ala315Ala	synonymous_variant	Exon 8 of 37		NP_001073948.2	Q8N1W1-6
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		Q8N1W1-1

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

GnomAD3 exomes

AF:

0.551

AC:

128889

AN:

233804

Hom.:

36140

AF XY:

0.543

AC XY:

68532

AN XY:

126096

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 SAS exome

AF:

0.552

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

Gnomad4 AFR exome

AF:

0.794

Gnomad4 AMR exome

AF:

0.584

Gnomad4 ASJ exome

AF:

0.438

Gnomad4 EAS exome

AF:

0.485

Gnomad4 SAS exome

AF:

0.554

Gnomad4 FIN exome

AF:

0.549

Gnomad4 NFE exome

AF:

0.524

Gnomad4 OTH exome

AF:

0.537

GnomAD4 genome

AF:

0.599

AC:

90867

AN:

151816

Hom.:

28349

Cov.:

AF XY:

0.598

AC XY:

44371

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.791

Gnomad4 AMR

AF:

0.558

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.520

Gnomad4 SAS

AF:

0.565

Gnomad4 FIN

AF:

0.550

Gnomad4 NFE

AF:

0.516

Gnomad4 OTH

AF:

0.566

Alfa

AF:

0.530

Hom.:

43534

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

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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

DANN

Benign

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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