Variant 2-227532168-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004504.5(AGFG1):c.814+958T>C variant causes a intron change. The variant allele was found at a frequency of 0.00023 in 1,549,366 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 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

AGFG1
NM_004504.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.26

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]

AGFG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0063670874).

BP6

Variant 2-227532168-T-C is Benign according to our data. Variant chr2-227532168-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 726407.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGFG1	NM_004504.5 linkuse as main transcript	c.814+958T>C		intron_variant		ENST00000310078.13
AGFG1	NM_001135187.2 linkuse as main transcript	c.845T>C	p.Phe282Ser	missense_variant	7/14
AGFG1	NM_001135188.2 linkuse as main transcript	c.814+958T>C		intron_variant
AGFG1	NM_001135189.2 linkuse as main transcript	c.695-1381T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGFG1	ENST00000310078.13 linkuse as main transcript	c.814+958T>C		intron_variant		1	NM_004504.5	P4	P52594-1

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

212

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000272

AC:

AN:

154642

Hom.:

AF XY:

0.000146

AC XY:

AN XY:

82050

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000167

Gnomad OTH exome

AF:

0.000463

GnomAD4 exome

AF:

0.000104

AC:

145

AN:

1397024

Hom.:

Cov.:

AF XY:

0.0000682

AC XY:

AN XY:

689054

show subpopulations

Gnomad4 AFR exome

AF:

0.00363

Gnomad4 AMR exome

AF:

0.000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000928

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152342

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00498

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000390

Hom.:

Bravo

AF:

0.00162

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000421

AC:

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 submitter

clinical testing

Invitae

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.65

M_CAP

Benign

0.014

MetaRNN

Benign

0.0064

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.65

REVEL

Benign

0.044

Sift

Benign

0.053

Sift4G

Benign

0.27

Vest4

0.29

MVP

0.52

MPC

0.22

ClinPred

0.019

GERP RS

3.9

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over