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GeneBe

2-227534999-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004504.5(AGFG1):c.1179G>A(p.Ala393=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,612,882 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

AGFG1
NM_004504.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.54
Variant links:
Genes affected
AGFG1 (HGNC:5175): (ArfGAP with FG repeats 1) The protein encoded by this gene is related to nucleoporins, a class of proteins that mediate nucleocytoplasmic transport. The encoded protein binds the activation domain of the human immunodeficiency virus Rev protein when Rev is assembled onto its RNA target, and is required for the nuclear export of Rev-directed RNAs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-227534999-G-A is Benign according to our data. Variant chr2-227534999-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651961.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=-1.54 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGFG1NM_004504.5 linkuse as main transcriptc.1179G>A p.Ala393= synonymous_variant 8/13 ENST00000310078.13
AGFG1NM_001135187.2 linkuse as main transcriptc.1251G>A p.Ala417= synonymous_variant 9/14
AGFG1NM_001135188.2 linkuse as main transcriptc.1179G>A p.Ala393= synonymous_variant 8/13
AGFG1NM_001135189.2 linkuse as main transcriptc.1059G>A p.Ala353= synonymous_variant 7/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGFG1ENST00000310078.13 linkuse as main transcriptc.1179G>A p.Ala393= synonymous_variant 8/131 NM_004504.5 P4P52594-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000276
AC:
42
AN:
152058
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000459
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000566
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000315
AC:
79
AN:
250484
Hom.:
0
AF XY:
0.000325
AC XY:
44
AN XY:
135410
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000204
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000926
Gnomad NFE exome
AF:
0.000565
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000425
AC:
621
AN:
1460824
Hom.:
1
Cov.:
32
AF XY:
0.000400
AC XY:
291
AN XY:
726724
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.000225
Gnomad4 NFE exome
AF:
0.000508
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000276
AC:
42
AN:
152058
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.000459
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000566
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000491
Hom.:
0
Bravo
AF:
0.000344
EpiCase
AF:
0.000547
EpiControl
AF:
0.000476

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022AGFG1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
3.4
Dann
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs373217967; hg19: chr2-228399715; COSMIC: COSV100028457; COSMIC: COSV100028457; API