Genetic Variant FGF17:c.73-190C>T (chr8-22045924-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003867.4(FGF17):c.73-190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,494,844 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 33 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 24 hom. )

Consequence

FGF17
NM_003867.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.30

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 8-22045924-C-T is Benign according to our data. Variant chr8-22045924-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1195403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1660/152282) while in subpopulation AFR AF = 0.0386 (1605/41544). AF 95% confidence interval is 0.0371. There are 33 homozygotes in GnomAd4. There are 758 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1660 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.73-190C>T		intron	N/A	NP_003858.1	O60258-1
	FGF17	NM_001304478.1		c.73-223C>T		intron	N/A	NP_001291407.1	O60258-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FGF17	ENST00000359441.4	TSL:1 MANE Select	c.73-190C>T	intron	N/A	ENSP00000352414.3	O60258-1
FGF17	ENST00000518533.5	TSL:1	c.73-223C>T	intron	N/A	ENSP00000431041.1	O60258-2
FGF17	ENST00000524314.1	TSL:2	n.1253C>T	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1658

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00573

GnomAD2 exomes

AF:

0.00265

AC:

281

AN:

105996

AF XY:

0.00231

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000968

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00101

AC:

1351

AN:

1342562

Hom.:

Cov.:

AF XY:

0.000884

AC XY:

580

AN XY:

656160

show subpopulations

African (AFR)

AF:

0.0371

AC:

1137

AN:

30610

American (AMR)

AF:

0.00145

AC:

AN:

32424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21580

East Asian (EAS)

AF:

0.0000285

AC:

AN:

35092

South Asian (SAS)

AF:

0.000144

AC:

AN:

69578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39812

Middle Eastern (MID)

AF:

0.00147

AC:

AN:

5446

European-Non Finnish (NFE)

AF:

0.0000257

AC:

AN:

1052196

Other (OTH)

AF:

0.00217

AC:

121

AN:

55824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0109

AC:

1660

AN:

152282

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

758

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0386

AC:

1605

AN:

41544

American (AMR)

AF:

0.00209

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68024

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

166

250

333

416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00556

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.10

(source)

DANN

Benign

0.46

PhyloP100

-1.3

Mutation Taster

=100/0

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