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GeneBe

2-235494818-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001037131.3(AGAP1):c.132C>T(p.Asn44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,579,606 control chromosomes in the GnomAD database, including 749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 54 hom., cov: 29)
Exomes 𝑓: 0.028 ( 695 hom. )

Consequence

AGAP1
NM_001037131.3 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.48
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 -13 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=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-235494818-C-T is Benign according to our data. Variant chr2-235494818-C-T is described in ClinVar as [Benign]. Clinvar id is 2013594.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=3.48 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0202 (3065/151520) while in subpopulation NFE AF= 0.0319 (2159/67760). AF 95% confidence interval is 0.0307. There are 54 homozygotes in gnomad4. There are 1382 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 54 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGAP1NM_001037131.3 linkuse as main transcriptc.132C>T p.Asn44= synonymous_variant 1/18 ENST00000304032.13
AGAP1NM_014914.5 linkuse as main transcriptc.132C>T p.Asn44= synonymous_variant 1/17
AGAP1NM_001244888.2 linkuse as main transcriptc.132C>T p.Asn44= synonymous_variant 1/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGAP1ENST00000304032.13 linkuse as main transcriptc.132C>T p.Asn44= synonymous_variant 1/185 NM_001037131.3 Q9UPQ3-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0202
AC:
3064
AN:
151414
Hom.:
54
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00600
Gnomad AMI
AF:
0.0549
Gnomad AMR
AF:
0.0244
Gnomad ASJ
AF:
0.0168
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00456
Gnomad FIN
AF:
0.00880
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0319
Gnomad OTH
AF:
0.0283
GnomAD3 exomes
AF:
0.0189
AC:
4268
AN:
225286
Hom.:
59
AF XY:
0.0191
AC XY:
2346
AN XY:
123008
show subpopulations
Gnomad AFR exome
AF:
0.00500
Gnomad AMR exome
AF:
0.0147
Gnomad ASJ exome
AF:
0.0159
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00431
Gnomad FIN exome
AF:
0.00779
Gnomad NFE exome
AF:
0.0310
Gnomad OTH exome
AF:
0.0236
GnomAD4 exome
AF:
0.0278
AC:
39712
AN:
1428086
Hom.:
695
Cov.:
32
AF XY:
0.0272
AC XY:
19321
AN XY:
710374
show subpopulations
Gnomad4 AFR exome
AF:
0.00448
Gnomad4 AMR exome
AF:
0.0162
Gnomad4 ASJ exome
AF:
0.0159
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.00463
Gnomad4 FIN exome
AF:
0.00963
Gnomad4 NFE exome
AF:
0.0330
Gnomad4 OTH exome
AF:
0.0227
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0202
AC:
3065
AN:
151520
Hom.:
54
Cov.:
29
AF XY:
0.0187
AC XY:
1382
AN XY:
74078
show subpopulations
Gnomad4 AFR
AF:
0.00599
Gnomad4 AMR
AF:
0.0244
Gnomad4 ASJ
AF:
0.0168
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00478
Gnomad4 FIN
AF:
0.00880
Gnomad4 NFE
AF:
0.0319
Gnomad4 OTH
AF:
0.0280
Alfa
AF:
0.0257
Hom.:
38
Bravo
AF:
0.0217

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 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
12
Dann
Uncertain
0.98
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: rs8178993; hg19: chr2-236403462; API