Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_173728.4(ARHGEF15):c.54G>A(p.Arg18Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,412,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ARHGEF15
NM_173728.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.381

Publications

1 publications found

Variant links:

Genes affected

ARHGEF15 (HGNC:15590): (Rho guanine nucleotide exchange factor 15) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

ARHGEF15 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ARHGEF15 links:

ENSG00000226871 (HGNC:):

ENSG00000226871 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-8312093-G-A is Benign according to our data. Variant chr17-8312093-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 530551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.381 with no splicing effect.

BS2

High AC in GnomAd4 at 240 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF15	NM_173728.4	MANE Select	c.54G>A	p.Arg18Arg	synonymous	Exon 2 of 16	NP_776089.2
	ARHGEF15	NM_025014.2		c.54G>A	p.Arg18Arg	synonymous	Exon 2 of 16	NP_079290.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARHGEF15	ENST00000361926.8	TSL:1 MANE Select	c.54G>A	p.Arg18Arg	synonymous	Exon 2 of 16	ENSP00000355026.3
ARHGEF15	ENST00000421050.2	TSL:1	c.54G>A	p.Arg18Arg	synonymous	Exon 2 of 16	ENSP00000412505.1
ARHGEF15	ENST00000579439.5	TSL:5	c.54G>A	p.Arg18Arg	synonymous	Exon 2 of 3	ENSP00000464540.1

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

239

AN:

112422

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00827

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000619

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000182

Gnomad OTH

AF:

0.000700

GnomAD2 exomes

AF:

0.000380

AC:

AN:

165958

AF XY:

0.000220

show subpopulations

Gnomad AFR exome

AF:

0.00526

Gnomad AMR exome

AF:

0.000107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

190

AN:

1300260

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

640268

show subpopulations

African (AFR)

AF:

0.00582

AC:

163

AN:

27988

American (AMR)

AF:

0.000135

AC:

AN:

29594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20380

East Asian (EAS)

AF:

0.00

AC:

AN:

33268

South Asian (SAS)

AF:

0.00

AC:

AN:

55316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5108

European-Non Finnish (NFE)

AF:

0.00000292

AC:

AN:

1028680

Other (OTH)

AF:

0.000380

AC:

AN:

52610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00213

AC:

240

AN:

112438

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

103

AN XY:

53780

show subpopulations

African (AFR)

AF:

0.00829

AC:

232

AN:

27994

American (AMR)

AF:

0.000619

AC:

AN:

9698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2800

East Asian (EAS)

AF:

0.00

AC:

AN:

4012

South Asian (SAS)

AF:

0.00

AC:

AN:

3454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

170

European-Non Finnish (NFE)

AF:

0.0000182

AC:

AN:

54910

Other (OTH)

AF:

0.000697

AC:

AN:

1434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00141

Hom.:

Bravo

AF:

0.00206

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARHGEF15-related disorder (1)

Developmental and epileptic encephalopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

0.38

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

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

rs138484229

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over