Genetic Variant FGF17:c.72+7G>A (chr8-22043188-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003867.4(FGF17):c.72+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,613,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

FGF17
NM_003867.4 splice_region, intron

Scores

Splicing: ADA: 0.00005038

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.86

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 8-22043188-G-A is Benign according to our data. Variant chr8-22043188-G-A is described in ClinVar as Benign. ClinVar VariationId is 745035.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 225 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.72+7G>A		splice_region intron	N/A	NP_003858.1	O60258-1
	FGF17	NM_001304478.1		c.72+7G>A		splice_region intron	N/A	NP_001291407.1	O60258-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF17	ENST00000359441.4	TSL:1 MANE Select	c.72+7G>A		splice_region intron	N/A	ENSP00000352414.3	O60258-1
	FGF17	ENST00000518533.5	TSL:1	c.72+7G>A		splice_region intron	N/A	ENSP00000431041.1	O60258-2

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00478

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000344

AC:

AN:

249762

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.00414

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1460920

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

105

AN XY:

726774

show subpopulations

African (AFR)

AF:

0.00475

AC:

159

AN:

33478

American (AMR)

AF:

0.000358

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52606

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111936

Other (OTH)

AF:

0.000563

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.00148

AC:

225

AN:

152282

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00479

AC:

199

AN:

41558

American (AMR)

AF:

0.00124

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68016

Other (OTH)

AF:

0.00142

AC:

AN:

2116

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

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:

0.000689

Hom.:

Bravo

AF:

0.00149

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance: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

-0.75

CADD

Benign

0.18

(source)

DANN

Benign

0.79

PhyloP100

-1.9

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000050

dbscSNV1_RF

Benign

0.032

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

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