rs72796308

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021226.4(ARHGAP22):​c.660-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,602,532 control chromosomes in the GnomAD database, including 9,569 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 904 hom., cov: 33)
Exomes 𝑓: 0.11 ( 8665 hom. )

Consequence

ARHGAP22
NM_021226.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00002077
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.250

Publications

3 publications found
Variant links:
Genes affected
ARHGAP22 (HGNC:30320): (Rho GTPase activating protein 22) This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP22NM_021226.4 linkc.660-7C>T splice_region_variant, intron_variant Intron 5 of 9 ENST00000249601.9 NP_067049.2 Q7Z5H3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP22ENST00000249601.9 linkc.660-7C>T splice_region_variant, intron_variant Intron 5 of 9 1 NM_021226.4 ENSP00000249601.4 Q7Z5H3-1

Frequencies

GnomAD3 genomes
AF:
0.108
AC:
16388
AN:
152156
Hom.:
905
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.116
Gnomad AMI
AF:
0.240
Gnomad AMR
AF:
0.0751
Gnomad ASJ
AF:
0.0971
Gnomad EAS
AF:
0.0610
Gnomad SAS
AF:
0.106
Gnomad FIN
AF:
0.138
Gnomad MID
AF:
0.0981
Gnomad NFE
AF:
0.108
Gnomad OTH
AF:
0.0982
GnomAD2 exomes
AF:
0.0970
AC:
23540
AN:
242722
AF XY:
0.0990
show subpopulations
Gnomad AFR exome
AF:
0.118
Gnomad AMR exome
AF:
0.0422
Gnomad ASJ exome
AF:
0.0822
Gnomad EAS exome
AF:
0.0619
Gnomad FIN exome
AF:
0.136
Gnomad NFE exome
AF:
0.107
Gnomad OTH exome
AF:
0.0942
GnomAD4 exome
AF:
0.107
AC:
155547
AN:
1450258
Hom.:
8665
Cov.:
32
AF XY:
0.107
AC XY:
77318
AN XY:
720194
show subpopulations
African (AFR)
AF:
0.111
AC:
3695
AN:
33368
American (AMR)
AF:
0.0468
AC:
2073
AN:
44342
Ashkenazi Jewish (ASJ)
AF:
0.0830
AC:
2140
AN:
25772
East Asian (EAS)
AF:
0.0512
AC:
2023
AN:
39530
South Asian (SAS)
AF:
0.112
AC:
9569
AN:
85204
European-Finnish (FIN)
AF:
0.137
AC:
7038
AN:
51536
Middle Eastern (MID)
AF:
0.0913
AC:
489
AN:
5354
European-Non Finnish (NFE)
AF:
0.110
AC:
121871
AN:
1105282
Other (OTH)
AF:
0.111
AC:
6649
AN:
59870
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
7269
14537
21806
29074
36343
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4462
8924
13386
17848
22310
<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:
0.108
AC:
16397
AN:
152274
Hom.:
904
Cov.:
33
AF XY:
0.109
AC XY:
8128
AN XY:
74454
show subpopulations
African (AFR)
AF:
0.116
AC:
4820
AN:
41550
American (AMR)
AF:
0.0749
AC:
1146
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.0971
AC:
337
AN:
3472
East Asian (EAS)
AF:
0.0607
AC:
315
AN:
5188
South Asian (SAS)
AF:
0.107
AC:
515
AN:
4830
European-Finnish (FIN)
AF:
0.138
AC:
1462
AN:
10614
Middle Eastern (MID)
AF:
0.0952
AC:
28
AN:
294
European-Non Finnish (NFE)
AF:
0.108
AC:
7350
AN:
68006
Other (OTH)
AF:
0.0976
AC:
206
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
781
1561
2342
3122
3903
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
188
376
564
752
940
<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:
0.0623
Hom.:
90
Bravo
AF:
0.104
Asia WGS
AF:
0.0730
AC:
255
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.3
DANN
Benign
0.54
PhyloP100
-0.25
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000021
dbscSNV1_RF
Benign
0.0
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

Other links and lift over

dbSNP: rs72796308; hg19: chr10-49663184; COSMIC: COSV50963829; COSMIC: COSV50963829; API