Genetic Variant AGGF1:p.Lys28Lys (chr5-77030850-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_018046.5(AGGF1):c.84G>A(p.Lys28Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,612,818 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 42 hom. )

Consequence

AGGF1
NM_018046.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.917

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 5-77030850-G-A is Benign according to our data. Variant chr5-77030850-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3257612.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.917 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGGF1	NM_018046.5	MANE Select	c.84G>A	p.Lys28Lys	synonymous	Exon 1 of 14	NP_060516.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGGF1	ENST00000312916.12	TSL:1 MANE Select	c.84G>A	p.Lys28Lys	synonymous	Exon 1 of 14	ENSP00000316109.7	Q8N302-1
AGGF1	ENST00000506806.1	TSL:1	c.84G>A	p.Lys28Lys	synonymous	Exon 1 of 3	ENSP00000424733.1	Q8N302-3
AGGF1	ENST00000502408.1	TSL:1	n.197+243G>A		intron	N/A	ENSP00000420874.1	H0Y8F8

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

497

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00569

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00334

AC:

813

AN:

243684

AF XY:

0.00345

show subpopulations

Gnomad AFR exome

AF:

0.000632

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00395

Gnomad NFE exome

AF:

0.00598

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00618

AC:

9021

AN:

1460432

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

4378

AN XY:

726570

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33474

American (AMR)

AF:

0.00157

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000842

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00363

AC:

189

AN:

52122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00756

AC:

8408

AN:

1111904

Other (OTH)

AF:

0.00494

AC:

298

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

590

1181

1771

2362

2952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.00326

AC:

497

AN:

152386

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

250

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.000817

AC:

AN:

41598

American (AMR)

AF:

0.00176

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00376

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00569

AC:

387

AN:

68036

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00276

Hom.:

Bravo

AF:

0.00326

EpiCase

AF:

0.00485

EpiControl

AF:

0.00516

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.92

PromoterAI

-0.10

Neutral

(source)

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over