8-22045805-G-A

Position:

• chr8-22045805-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003867.4(FGF17):​c.73-309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,289,656 control chromosomes in the GnomAD database, including 31,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4373 hom., cov: 33)
  • Exomes 𝑓: 0.22 (27531 hom.)
• Consequence: FGF17 NM_003867.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.214

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-22045805-G-A is Benign according to our data. Variant chr8-22045805-G-A is described in ClinVar as [Benign]. Clinvar id is 1182914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF17	NM_003867.4	c.73-309G>A		intron_variant		ENST00000359441.4	NP_003858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF17	ENST00000359441.4	c.73-309G>A		intron_variant		1	NM_003867.4	ENSP00000352414.3
FGF17	ENST00000518533.5	c.73-342G>A		intron_variant		1		ENSP00000431041.1
FGF17	ENST00000524314.1	n.1134G>A		non_coding_transcript_exon_variant	1/3	2
FGF17	ENST00000521709.1	n.451-342G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35855 AN: 152020 Hom.: 4368 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.218 AC: 248440 AN: 1137518 Hom.: 27531 Cov.: 34 AF XY: 0.218 AC XY: 119194 AN XY: 545724

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.236 AC: 35888 AN: 152138 Hom.: 4373 Cov.: 33 AF XY: 0.239 AC XY: 17791 AN XY: 74364

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.248

Alfa AF: 0.231 Hom.: 5528

Bravo AF: 0.238

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs3176292; hg19: chr8-21903316;