rs12720208

Variant names:

• chr8-16992890-G-A
• rs12720208
• NM_019851.3:c.*182C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 64 publications found

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]

FGF20 Gene-Disease associations (from GenCC):

• bilateral renal agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal hypodysplasia/aplasia 2

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.*182C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.*182C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.*182C>T		downstream_gene_variant		5		ENSP00000428072.1

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

African (AFR) AF: 0.0149 AC: 200 AN: 13406

American (AMR) AF: 0.0452 AC: 794 AN: 17556

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 457 AN: 13580

East Asian (EAS) AF: 0.00395 AC: 119 AN: 30098

South Asian (SAS) AF: 0.0484 AC: 2203 AN: 45506

European-Finnish (FIN) AF: 0.0365 AC: 1022 AN: 27964

Middle Eastern (MID) AF: 0.0316 AC: 79 AN: 2500

European-Non Finnish (NFE) AF: 0.0880 AC: 29579 AN: 336078

Other (OTH) AF: 0.0621 AC: 1711 AN: 27534

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

African (AFR) AF: 0.0169 AC: 703 AN: 41506

American (AMR) AF: 0.0531 AC: 811 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3472

East Asian (EAS) AF: 0.00658 AC: 34 AN: 5170

South Asian (SAS) AF: 0.0494 AC: 238 AN: 4820

European-Finnish (FIN) AF: 0.0350 AC: 370 AN: 10586

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0848 AC: 5766 AN: 67988

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0676 Hom.: 420

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20427658, 18252210, 30241547) -

Parkinson disease, late-onset Uncertain:1

Feb 15, 2009

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.48
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12720208; hg19: chr8-16850399;