rs199663714

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_173728.4(ARHGEF15):c.80G>A(p.Arg27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000616 in 1,379,258 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R27P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ARHGEF15
NM_173728.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.38

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030038357).

BS2

High AC in GnomAd4 at 46 AD,Unknown 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF15	NM_173728.4	MANE Select	c.80G>A	p.Arg27His	missense	Exon 2 of 16	NP_776089.2
	ARHGEF15	NM_025014.2		c.80G>A	p.Arg27His	missense	Exon 2 of 16	NP_079290.1	O94989

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGEF15	ENST00000361926.8	TSL:1 MANE Select	c.80G>A	p.Arg27His	missense	Exon 2 of 16	ENSP00000355026.3	O94989
ARHGEF15	ENST00000421050.2	TSL:1	c.80G>A	p.Arg27His	missense	Exon 2 of 16	ENSP00000412505.1	O94989
ARHGEF15	ENST00000852584.1		c.80G>A	p.Arg27His	missense	Exon 2 of 16	ENSP00000522643.1

Frequencies

GnomAD3 genomes

AF:

0.000457

AC:

AN:

100590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000816

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00546

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:

0.00

Gnomad OTH

AF:

0.00154

GnomAD2 exomes

AF:

0.0000494

AC:

AN:

182036

AF XY:

0.0000299

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000195

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000114

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1278664

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

628156

show subpopulations

African (AFR)

AF:

0.0000360

AC:

AN:

27756

American (AMR)

AF:

0.000831

AC:

AN:

31294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20878

East Asian (EAS)

AF:

0.00

AC:

AN:

31492

South Asian (SAS)

AF:

0.00

AC:

AN:

56636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45946

Middle Eastern (MID)

AF:

0.000398

AC:

AN:

5026

European-Non Finnish (NFE)

AF:

0.00000297

AC:

AN:

1008640

Other (OTH)

AF:

0.000137

AC:

AN:

50996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.571

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:

0.000457

AC:

AN:

100594

Hom.:

Cov.:

AF XY:

0.000489

AC XY:

AN XY:

47044

show subpopulations

African (AFR)

AF:

0.0000815

AC:

AN:

24544

American (AMR)

AF:

0.00545

AC:

AN:

7704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2722

East Asian (EAS)

AF:

0.00

AC:

AN:

3572

South Asian (SAS)

AF:

0.00

AC:

AN:

3260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

112

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51708

Other (OTH)

AF:

0.00153

AC:

AN:

1304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

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:

0.0000454

Hom.:

Bravo

AF:

0.000797

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.0

PhyloP100

3.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.090

REVEL

Benign

0.24

Sift

Uncertain

0.0010

Sift4G

Benign

0.075

Polyphen

1.0

Vest4

0.39

MVP

0.87

MPC

0.50

ClinPred

0.27

GERP RS

5.0

Varity_R

0.10

gMVP

0.29

Mutation Taster

=97/3

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over