rs12720208

Positions:

• chr8-16992890-G-A

Variant summary

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

The NM_019851.3(FGF20):​c.*182C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 666,364 control chromosomes in the GnomAD database, including 1,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (294 hom., cov: 32)
  • Exomes 𝑓: 0.070 (1527 hom.)
• Consequence: FGF20 NM_019851.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: 0.460

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-16992890-G-A is Benign according to our data. Variant chr8-16992890-G-A is described in ClinVar as [Benign]. Clinvar id is 4885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF20	NM_019851.3	c.*182C>T		3_prime_UTR_variant	3/3	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.*182C>T		3_prime_UTR_variant	3/3	1	NM_019851.3	ENSP00000180166	P1

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8291 AN: 152024 Hom.: 294 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.00675

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0703 AC: 36164 AN: 514222 Hom.: 1527 Cov.: 7 AF XY: 0.0696 AC XY: 18764 AN XY: 269530

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.0452

Gnomad4 ASJ exome AF: 0.0337

Gnomad4 EAS exome AF: 0.00395

Gnomad4 SAS exome AF: 0.0484

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0880

Gnomad4 OTH exome AF: 0.0621

GnomAD4 genome AF: 0.0545 AC: 8288 AN: 152142 Hom.: 294 Cov.: 32 AF XY: 0.0517 AC XY: 3847 AN XY: 74374

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.0531

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.00658

Gnomad4 SAS AF: 0.0494

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.0848

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0757 Hom.: 308

Bravo AF: 0.0534

Asia WGS AF: 0.0310 AC: 107 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	This variant is associated with the following publications: (PMID: 20427658, 18252210, 30241547) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Parkinson disease, late-onset Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Feb 15, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
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: rs12720208; hg19: chr8-16850399;