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GeneBe

10-48446502-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021226.4(ARHGAP22):c.1986G>A(p.Ala662=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,614,202 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 147 hom., cov: 32)
Exomes 𝑓: 0.0030 ( 152 hom. )

Consequence

ARHGAP22
NM_021226.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.89
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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-48446502-C-T is Benign according to our data. Variant chr10-48446502-C-T is described in ClinVar as [Benign]. Clinvar id is 776509.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.89 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARHGAP22NM_021226.4 linkuse as main transcriptc.1986G>A p.Ala662= synonymous_variant 10/10 ENST00000249601.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARHGAP22ENST00000249601.9 linkuse as main transcriptc.1986G>A p.Ala662= synonymous_variant 10/101 NM_021226.4 P4Q7Z5H3-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0235
AC:
3581
AN:
152192
Hom.:
147
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0791
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00877
Gnomad ASJ
AF:
0.00260
Gnomad EAS
AF:
0.0204
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.0182
GnomAD3 exomes
AF:
0.00793
AC:
1993
AN:
251480
Hom.:
66
AF XY:
0.00614
AC XY:
834
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0824
Gnomad AMR exome
AF:
0.00359
Gnomad ASJ exome
AF:
0.000893
Gnomad EAS exome
AF:
0.0260
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00293
GnomAD4 exome
AF:
0.00302
AC:
4417
AN:
1461892
Hom.:
152
Cov.:
32
AF XY:
0.00265
AC XY:
1926
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0820
Gnomad4 AMR exome
AF:
0.00362
Gnomad4 ASJ exome
AF:
0.00149
Gnomad4 EAS exome
AF:
0.0241
Gnomad4 SAS exome
AF:
0.000313
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000962
Gnomad4 OTH exome
AF:
0.00604
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0236
AC:
3587
AN:
152310
Hom.:
147
Cov.:
32
AF XY:
0.0224
AC XY:
1665
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0791
Gnomad4 AMR
AF:
0.00869
Gnomad4 ASJ
AF:
0.00260
Gnomad4 EAS
AF:
0.0200
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.0175
Alfa
AF:
0.0106
Hom.:
27
Bravo
AF:
0.0272
Asia WGS
AF:
0.0110
AC:
38
AN:
3476
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 27, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
0.47
Dann
Benign
0.51
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76208937; hg19: chr10-49654545; API