Genetic Variant FGF17:p.Pro29Pro (chr8-22046128-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_003867.4(FGF17):c.87G>A(p.Pro29Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P29P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

FGF17
NM_003867.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.75

Publications

0 publications found

Variant links:

Genes affected

FGF17 (HGNC:3673): (fibroblast growth factor 17) This gene encodes a member of the fibroblast growth factor (FGF) family. Member of the FGF family 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 protein is expressed during embryogenesis and in the adult cerebellum and cortex and may be essential for vascular growth and normal brain development. Mutations in this gene are the cause of hypogonadotropic hypogonadism 20 with or without anosmia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

FGF17 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 20 with or without anosmia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FGF17 links:

Genome browser will be placed here

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=-0.47).

BP7

Synonymous conserved (PhyloP=2.75 with no splicing effect.

BS2

High AC in GnomAdExome4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003867.4. 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
	FGF17	NM_003867.4	MANE Select	c.87G>A	p.Pro29Pro	synonymous	Exon 3 of 5	NP_003858.1	O60258-1
	FGF17	NM_001304478.1		c.73-19G>A		intron	N/A	NP_001291407.1	O60258-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF17	ENST00000359441.4	TSL:1 MANE Select	c.87G>A	p.Pro29Pro	synonymous	Exon 3 of 5	ENSP00000352414.3	O60258-1
FGF17	ENST00000518533.5	TSL:1	c.73-19G>A		intron	N/A	ENSP00000431041.1	O60258-2
FGF17	ENST00000524314.1	TSL:2	n.1457G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251416

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over