Menu
GeneBe

2-235709225-G-A

Variant summary

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

The NM_001037131.3(AGAP1):c.210G>A(p.Pro70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,930 control chromosomes in the GnomAD database, including 2,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.070 ( 1275 hom., cov: 32)
Exomes 𝑓: 0.0075 ( 1167 hom. )

Consequence

AGAP1
NM_001037131.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.65
Variant links:
Genes affected
AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Genome browser will be placed here

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=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-235709225-G-A is Benign according to our data. Variant chr2-235709225-G-A is described in ClinVar as [Benign]. Clinvar id is 2003469.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=-3.65 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 = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGAP1NM_001037131.3 linkuse as main transcriptc.210G>A p.Pro70= synonymous_variant 2/18 ENST00000304032.13
AGAP1NM_014914.5 linkuse as main transcriptc.210G>A p.Pro70= synonymous_variant 2/17
AGAP1NM_001244888.2 linkuse as main transcriptc.210G>A p.Pro70= synonymous_variant 2/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGAP1ENST00000304032.13 linkuse as main transcriptc.210G>A p.Pro70= synonymous_variant 2/185 NM_001037131.3 Q9UPQ3-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0703
AC:
10678
AN:
151986
Hom.:
1275
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0272
Gnomad ASJ
AF:
0.00635
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000831
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.00106
Gnomad OTH
AF:
0.0551
GnomAD3 exomes
AF:
0.0186
AC:
4676
AN:
251444
Hom.:
523
AF XY:
0.0135
AC XY:
1836
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.246
Gnomad AMR exome
AF:
0.0126
Gnomad ASJ exome
AF:
0.00506
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000653
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000870
Gnomad OTH exome
AF:
0.0108
GnomAD4 exome
AF:
0.00754
AC:
11017
AN:
1461826
Hom.:
1167
Cov.:
31
AF XY:
0.00649
AC XY:
4723
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.250
Gnomad4 AMR exome
AF:
0.0145
Gnomad4 ASJ exome
AF:
0.00582
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000568
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000645
Gnomad4 OTH exome
AF:
0.0168
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0703
AC:
10688
AN:
152104
Hom.:
1275
Cov.:
32
AF XY:
0.0677
AC XY:
5031
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.243
Gnomad4 AMR
AF:
0.0272
Gnomad4 ASJ
AF:
0.00635
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000832
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00106
Gnomad4 OTH
AF:
0.0546
Alfa
AF:
0.0320
Hom.:
267
Bravo
AF:
0.0801
Asia WGS
AF:
0.0110
AC:
39
AN:
3478
EpiCase
AF:
0.00120
EpiControl
AF:
0.000889

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 testingInvitaeJan 22, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
5.2
Dann
Benign
0.87
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: rs8178995; hg19: chr2-236617869; COSMIC: COSV58323032; API