8-16998633-G-C

Variant names:

• chr8-16998633-G-C
• rs17515020
• NM_019851.3:c.287-2875C>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.287-2875C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,054 control chromosomes in the GnomAD database, including 2,649 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 0.17 (2649 hom., cov: 32)
• Consequence: FGF20 NM_019851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 1 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.287-2875C>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.287-2875C>G		intron_variant	Intron 1 of 2	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.93+3114C>G		intron_variant	Intron 1 of 1	5		ENSP00000428072.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25899 AN: 151936 Hom.: 2631 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.171 AC: 25955 AN: 152054 Hom.: 2649 Cov.: 32 AF XY: 0.173 AC XY: 12860 AN XY: 74318

African (AFR) AF: 0.216 AC: 8937 AN: 41458

American (AMR) AF: 0.234 AC: 3575 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2403 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4820

European-Finnish (FIN) AF: 0.0977 AC: 1031 AN: 10556

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8135 AN: 67986

Other (OTH) AF: 0.172 AC: 363 AN: 2112

Alfa AF: 0.0672 Hom.: 77

Bravo AF: 0.183

Asia WGS AF: 0.321 AC: 1116 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		0.74
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: rs17515020; hg19: chr8-16856142;