chr17-8316082-G-A

Variant names:

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.1638G>A(p.Arg546Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,602,936 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R546R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 3 hom. )

Consequence

ARHGEF15
NM_173728.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0310

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=-0.49).

BP6

Variant 17-8316082-G-A is Benign according to our data. Variant chr17-8316082-G-A is described in ClinVar as Benign. ClinVar VariationId is 461428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.031 with no splicing effect.

BS2

High AC in GnomAd4 at 284 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF15	NM_173728.4 link	c.1638G>A	p.Arg546Arg	synonymous_variant	Exon 9 of 16	ENST00000361926.8	NP_776089.2	O94989A0A0S2Z547

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARHGEF15	ENST00000361926.8 link	c.1638G>A	p.Arg546Arg	synonymous_variant	Exon 9 of 16	1	NM_173728.4	ENSP00000355026.3	O94989
ARHGEF15	ENST00000421050.2 link	c.1638G>A	p.Arg546Arg	synonymous_variant	Exon 9 of 16	1		ENSP00000412505.1	O94989
ARHGEF15	ENST00000647883.1 link	c.1101G>A	p.Arg367Arg	synonymous_variant	Exon 6 of 13			ENSP00000498197.1	A0A3B3IUF8
ENSG00000226871	ENST00000820533.1 link	n.313+2484C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000469

AC:

110

AN:

234584

AF XY:

0.000396

show subpopulations

Gnomad AFR exome

AF:

0.00435

Gnomad AMR exome

AF:

0.000826

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000689

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.000855

GnomAD4 exome

AF:

0.000249

AC:

361

AN:

1450614

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

168

AN XY:

721952

show subpopulations

African (AFR)

AF:

0.00688

AC:

230

AN:

33414

American (AMR)

AF:

0.000810

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44030

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1111218

Other (OTH)

AF:

0.000731

AC:

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00186

AC:

284

AN:

152322

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00652

AC:

271

AN:

41586

American (AMR)

AF:

0.000327

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000844

Hom.:

Bravo

AF:

0.00198

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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

-0.49

CADD

Benign

7.7

(source)

DANN

Benign

0.95

PhyloP100

0.031

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over