dbSNP rs144703076: ARHGEF15:p.Ala68Ala (chr17-8312243-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_173728.4(ARHGEF15):c.204A>G(p.Ala68Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000479 in 1,378,452 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 0.00011 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ARHGEF15
NM_173728.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.73

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.032).

BP6

Variant 17-8312243-A-G is Benign according to our data. Variant chr17-8312243-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 412678.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BS2

High AC in GnomAd4 at 14 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF15	NM_173728.4	MANE Select	c.204A>G	p.Ala68Ala	synonymous	Exon 2 of 16	NP_776089.2
	ARHGEF15	NM_025014.2		c.204A>G	p.Ala68Ala	synonymous	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.204A>G	p.Ala68Ala	synonymous	Exon 2 of 16	ENSP00000355026.3	O94989
ARHGEF15	ENST00000421050.2	TSL:1	c.204A>G	p.Ala68Ala	synonymous	Exon 2 of 16	ENSP00000412505.1	O94989
ARHGEF15	ENST00000852584.1		c.204A>G	p.Ala68Ala	synonymous	Exon 2 of 16	ENSP00000522643.1

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

129648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000574

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000312

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000181

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000787

AC:

AN:

203254

AF XY:

0.0000831

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000352

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000416

AC:

AN:

1248804

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

617114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28752

American (AMR)

AF:

0.0000552

AC:

AN:

36252

Ashkenazi Jewish (ASJ)

AF:

0.0000540

AC:

AN:

18510

East Asian (EAS)

AF:

0.00

AC:

AN:

35714

South Asian (SAS)

AF:

0.00

AC:

AN:

73234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42198

Middle Eastern (MID)

AF:

0.000624

AC:

AN:

4804

European-Non Finnish (NFE)

AF:

0.0000406

AC:

AN:

960078

Other (OTH)

AF:

0.000142

AC:

AN:

49262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000108

AC:

AN:

129648

Hom.:

Cov.:

AF XY:

0.0000965

AC XY:

AN XY:

62202

show subpopulations

African (AFR)

AF:

0.0000574

AC:

AN:

34822

American (AMR)

AF:

0.00

AC:

AN:

12382

Ashkenazi Jewish (ASJ)

AF:

0.000312

AC:

AN:

3202

East Asian (EAS)

AF:

0.00

AC:

AN:

4526

South Asian (SAS)

AF:

0.00

AC:

AN:

3404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000181

AC:

AN:

60728

Other (OTH)

AF:

0.00

AC:

AN:

1770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.0000504

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

(source)

DANN

Benign

0.47

PhyloP100

-1.7

Mutation Taster

=100/0

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