8-17000966-G-C

Variant names:

• chr8-17000966-G-C
• rs1989754
• NM_019851.3:c.286+781C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019851.3(FGF20):​c.286+781C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,308 control chromosomes in the GnomAD database, including 11,494 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 0.37 (11494 hom., cov: 29)
• Consequence: FGF20 NM_019851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.286+781C>G		intron_variant	Intron 1 of 2	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.286+781C>G		intron_variant	Intron 1 of 2	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.93+781C>G		intron_variant	Intron 1 of 1	5		ENSP00000428072.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55849 AN: 151190 Hom.: 11491 Cov.: 29

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.369 AC: 55860 AN: 151308 Hom.: 11494 Cov.: 29 AF XY: 0.376 AC XY: 27717 AN XY: 73800

African (AFR) AF: 0.172 AC: 7097 AN: 41320

American (AMR) AF: 0.446 AC: 6741 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1836 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2625 AN: 5088

South Asian (SAS) AF: 0.482 AC: 2313 AN: 4796

European-Finnish (FIN) AF: 0.462 AC: 4765 AN: 10312

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 28972 AN: 67904

Other (OTH) AF: 0.412 AC: 864 AN: 2096

Alfa AF: 0.384 Hom.: 1481

Bravo AF: 0.361

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	15
DANN	Benign	0.57
PhyloP100		0.42
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: rs1989754; hg19: chr8-16858475;