rs73118524

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001177693.2(ARHGEF28):c.964-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,612,788 control chromosomes in the GnomAD database, including 14,150 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 5359 hom., cov: 32)

Exomes 𝑓: 0.075 ( 8791 hom. )

Consequence

ARHGEF28
NM_001177693.2 splice_region, intron

Scores

Splicing: ADA: 0.00003687

Clinical Significance

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

Conservation

PhyloP100: -0.691

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-73795324-C-T is Benign according to our data. Variant chr5-73795324-C-T is described in ClinVar as [Benign]. Clinvar id is 257380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-73795324-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF28	NM_001177693.2 link	c.964-7C>T	splice_region_variant, intron_variant	Intron 8 of 35	ENST00000513042.7	NP_001171164.1	Q8N1W1-1
ARHGEF28	NM_001080479.3 link	c.964-7C>T	splice_region_variant, intron_variant	Intron 8 of 36		NP_001073948.2	Q8N1W1-6
ARHGEF28	NM_001388078.1 link	c.964-7C>T	splice_region_variant, intron_variant	Intron 8 of 34		NP_001375007.1
ARHGEF28	NM_001388076.1 link	c.670-7C>T	splice_region_variant, intron_variant	Intron 7 of 34		NP_001375005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7 link	c.964-7C>T		splice_region_variant, intron_variant	Intron 8 of 35	5	NM_001177693.2	ENSP00000441436.1		Q8N1W1-1

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28698

AN:

151998

Hom.:

5343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0563

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0490

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.122

AC:

30264

AN:

248858

Hom.:

3587

AF XY:

0.113

AC XY:

15321

AN XY:

135032

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.0573

Gnomad NFE exome

AF:

0.0478

Gnomad OTH exome

AF:

0.0894

GnomAD4 exome

AF:

0.0746

AC:

109025

AN:

1460672

Hom.:

8791

Cov.:

AF XY:

0.0753

AC XY:

54730

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.490

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.0552

Gnomad4 NFE exome

AF:

0.0471

Gnomad4 OTH exome

AF:

0.0987

GnomAD4 genome

AF:

0.189

AC:

28765

AN:

152116

Hom.:

5359

Cov.:

AF XY:

0.189

AC XY:

14062

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.479

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.0441

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.0563

Gnomad4 NFE

AF:

0.0490

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.106

Hom.:

1062

Bravo

AF:

0.210

Asia WGS

AF:

0.258

AC:

896

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

Genome Diagnostics Laboratory, Amsterdam University 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

- -

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

-0.90

CADD

Benign

0.30

DANN

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.0

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