dbSNP rs1721082: FGF20:c.*449T>A (chr8-16992623-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019851.3(FGF20):c.*449T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,650 control chromosomes in the GnomAD database, including 37,848 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 0.69 ( 37789 hom., cov: 30)

Exomes 𝑓: 0.68 ( 59 hom. )

Consequence

FGF20
NM_019851.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

Publications

2 publications found

Variant links:

Genes affected

FGF20 (HGNC:3677): (fibroblast growth factor 20) The protein encoded by this gene is a member of the fibroblast growth factor family. The fibroblast growth factors possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene product is a secreted neurotrophic factor but lacks a typical signal peptide. It is expressed in normal brain, particularly the cerebellum, and may regulate central nervous system development and function. Homodimerization of this protein was shown to regulate its receptor binding activity and concentration gradient in the extracellular matrix. Genetic variations of this gene have been associated with Parkinson disease susceptibility. [provided by RefSeq, Oct 2009]

FGF20 Gene-Disease associations (from GenCC):

bilateral renal agenesis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
renal hypodysplasia/aplasia 2
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

FGF20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3 link	c.*449T>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6 link	c.*449T>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_019851.3	ENSP00000180166.5

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105126

AN:

151316

Hom.:

37774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.840

Gnomad AMR

AF:

0.684

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.702

GnomAD4 exome

AF:

0.680

AC:

151

AN:

222

Hom.:

Cov.:

AF XY:

0.650

AC XY:

AN XY:

120

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.667

AC:

AN:

European-Finnish (FIN)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.724

AC:

126

AN:

174

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.695

AC:

105177

AN:

151428

Hom.:

37789

Cov.:

AF XY:

0.699

AC XY:

51712

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.514

AC:

21231

AN:

41332

American (AMR)

AF:

0.684

AC:

10403

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

2843

AN:

3468

East Asian (EAS)

AF:

0.512

AC:

2641

AN:

5162

South Asian (SAS)

AF:

0.722

AC:

3471

AN:

4806

European-Finnish (FIN)

AF:

0.866

AC:

8888

AN:

10266

Middle Eastern (MID)

AF:

0.741

AC:

218

AN:

294

European-Non Finnish (NFE)

AF:

0.784

AC:

53247

AN:

67876

Other (OTH)

AF:

0.699

AC:

1469

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1495

2990

4485

5980

7475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.741

Hom.:

5325

Bravo

AF:

0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.58

(source)

DANN

Benign

0.53

PhyloP100

0.13

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