Genetic Variant AGGF1:p.Ile405Ile (chr5-77048174-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_018046.5(AGGF1):c.1215T>C(p.Ile405Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,606,922 control chromosomes in the GnomAD database, including 51,954 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4428 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47526 hom. )

Consequence

AGGF1
NM_018046.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

Publications

22 publications found

Variant links:

Genes affected

AGGF1 (HGNC:24684): (angiogenic factor with G-patch and FHA domains 1) This gene encodes an angiogenic factor that promotes proliferation of endothelial cells. Mutations in this gene are associated with a susceptibility to Klippel-Trenaunay syndrome. Pseudogenes of this gene are found on chromosomes 3, 4, 10 and 16.[provided by RefSeq, Sep 2010]

AGGF1 links:

ENSG00000285000 (HGNC:):

ENSG00000285000 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-0.047 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGGF1	NM_018046.5 link	c.1215T>C	p.Ile405Ile	synonymous_variant	Exon 7 of 14	ENST00000312916.12	NP_060516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGGF1	ENST00000312916.12 link	c.1215T>C	p.Ile405Ile	synonymous_variant	Exon 7 of 14	1	NM_018046.5	ENSP00000316109.7
ENSG00000285000	ENST00000646704.1 link	n.1080T>C		non_coding_transcript_exon_variant	Exon 7 of 16			ENSP00000495089.1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36469

AN:

151918

Hom.:

4430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.242

AC:

60912

AN:

251380

AF XY:

0.242

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.252

AC:

366727

AN:

1454886

Hom.:

47526

Cov.:

AF XY:

0.252

AC XY:

182219

AN XY:

724122

show subpopulations

African (AFR)

AF:

0.214

AC:

7130

AN:

33368

American (AMR)

AF:

0.279

AC:

12453

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

6141

AN:

26084

East Asian (EAS)

AF:

0.133

AC:

5252

AN:

39594

South Asian (SAS)

AF:

0.249

AC:

21444

AN:

86096

European-Finnish (FIN)

AF:

0.193

AC:

10322

AN:

53348

Middle Eastern (MID)

AF:

0.202

AC:

1110

AN:

5488

European-Non Finnish (NFE)

AF:

0.260

AC:

288133

AN:

1106110

Other (OTH)

AF:

0.245

AC:

14742

AN:

60096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

12756

25512

38267

51023

63779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9700

19400

29100

38800

48500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.240

AC:

36484

AN:

152036

Hom.:

4428

Cov.:

AF XY:

0.236

AC XY:

17568

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.224

AC:

9304

AN:

41466

American (AMR)

AF:

0.245

AC:

3742

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

834

AN:

3468

East Asian (EAS)

AF:

0.150

AC:

775

AN:

5156

South Asian (SAS)

AF:

0.254

AC:

1221

AN:

4814

European-Finnish (FIN)

AF:

0.195

AC:

2062

AN:

10560

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17774

AN:

67992

Other (OTH)

AF:

0.227

AC:

478

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1395

2790

4186

5581

6976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

7265

Bravo

AF:

0.242

Asia WGS

AF:

0.202

AC:

702

AN:

3478

EpiCase

AF:

0.255

EpiControl

AF:

0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.6

(source)

DANN

Benign

0.75

PhyloP100

-0.047

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over