rs17514985

Positions:

• chr8-17000197-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019851.3(FGF20):​c.286+1550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 152,166 control chromosomes in the GnomAD database, including 304 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 0.055 (304 hom., cov: 31)
• Consequence: FGF20 NM_019851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF20	NM_019851.3	c.286+1550A>G		intron_variant		ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.286+1550A>G		intron_variant		1	NM_019851.3	ENSP00000180166	P1
FGF20	ENST00000519941.1	c.94+1550A>G		intron_variant		5		ENSP00000428072

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8366 AN: 152048 Hom.: 304 Cov.: 31

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.00700

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0649

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0550 AC: 8362 AN: 152166 Hom.: 304 Cov.: 31 AF XY: 0.0522 AC XY: 3882 AN XY: 74382

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.00682

Gnomad4 SAS AF: 0.0486

Gnomad4 FIN AF: 0.0346

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0636 Hom.: 51

Bravo AF: 0.0541

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.78

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: rs17514985; hg19: chr8-16857706;