dbSNP rs1204926390: ARHGAP1:p.Arg234Gln (chr11-46680682-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_004308.5(ARHGAP1):c.701G>A(p.Arg234Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000312 in 1,601,730 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. R234W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ARHGAP1
NM_004308.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

Publications

2 publications found

Variant links:

Genes affected

ARHGAP1 (HGNC:673): (Rho GTPase activating protein 1) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]

ARHGAP1 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=0.3120843).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004308.5. 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
	ARHGAP1	NM_004308.5	MANE Select	c.701G>A	p.Arg234Gln	missense	Exon 8 of 13	NP_004299.1	Q07960

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP1	ENST00000311956.9	TSL:1 MANE Select	c.701G>A	p.Arg234Gln	missense	Exon 8 of 13	ENSP00000310491.4	Q07960
ARHGAP1	ENST00000526423.1	TSL:1	n.389G>A		non_coding_transcript_exon	Exon 3 of 8
ARHGAP1	ENST00000873835.1		c.866G>A	p.Arg289Gln	missense	Exon 8 of 13	ENSP00000543894.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151636

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

239032

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1450094

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720032

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33264

American (AMR)

AF:

0.0000226

AC:

AN:

44174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25356

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104916

Other (OTH)

AF:

0.00

AC:

AN:

59878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00000659

AC:

AN:

151636

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41214

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67916

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00000756

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

Benign

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Benign

0.082

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0079

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

6.4

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

REVEL

Benign

0.068

Sift

Benign

0.11

Sift4G

Benign

0.20

Polyphen

0.45

Vest4

0.35

MutPred

0.31

Gain of ubiquitination at K229 (P = 0.0239)

MVP

0.48

MPC

0.31

ClinPred

0.94

GERP RS

4.9

Varity_R

0.37

gMVP

0.48

Mutation Taster

=73/27

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

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