dbSNP rs748621506: ARHGEF17:p.Ser15Leu (chr11-73308682-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014786.4(ARHGEF17):c.44C>T(p.Ser15Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000723 in 1,520,516 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

ARHGEF17
NM_014786.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Publications

0 publications found

Variant links:

Genes affected

ARHGEF17 (HGNC:21726): (Rho guanine nucleotide exchange factor 17) Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within actin cytoskeleton organization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF17 links:

ARHGEF17-AS1 (HGNC:55485): (ARHGEF17 antisense RNA 1)

ARHGEF17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37689286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014786.4. 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
	ARHGEF17	NM_014786.4	MANE Select	c.44C>T	p.Ser15Leu	missense	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.680G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGEF17	ENST00000263674.4	TSL:1 MANE Select	c.44C>T	p.Ser15Leu	missense	Exon 1 of 21	ENSP00000263674.3	Q96PE2
ARHGEF17	ENST00000914587.1		c.44C>T	p.Ser15Leu	missense	Exon 1 of 20	ENSP00000584647.1
ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.680G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000261

AC:

AN:

115136

AF XY:

0.0000307

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000235

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000731

AC:

AN:

1368352

Hom.:

Cov.:

AF XY:

0.00000739

AC XY:

AN XY:

676488

show subpopulations

African (AFR)

AF:

0.0000358

AC:

AN:

27950

American (AMR)

AF:

0.00

AC:

AN:

33434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23986

East Asian (EAS)

AF:

0.0000327

AC:

AN:

30552

South Asian (SAS)

AF:

0.0000130

AC:

AN:

76848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4966

European-Non Finnish (NFE)

AF:

0.00000374

AC:

AN:

1069316

Other (OTH)

AF:

0.0000531

AC:

AN:

56480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000179

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.69

PhyloP100

4.2

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.64

REVEL

Benign

0.29

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0090

Polyphen

0.98

Vest4

0.37

MutPred

0.38

Loss of sheet (P = 0.0126)

MVP

0.56

MPC

1.0

ClinPred

0.45

GERP RS

3.7

PromoterAI

0.056

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.28

gMVP

0.59

Mutation Taster

=98/2

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