chr8-17001181-A-G

Variant names:

• chr8-17001181-A-G
• rs1989756
• NM_019851.3:c.286+566T>C

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+566T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,004 control chromosomes in the GnomAD database, including 66,971 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 0.94 (66971 hom., cov: 29)
• Consequence: FGF20 NM_019851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 2 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 = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.286+566T>C		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+566T>C		intron_variant	Intron 1 of 2	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.93+566T>C		intron_variant	Intron 1 of 1	5		ENSP00000428072.1

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142523 AN: 151886 Hom.: 66913 Cov.: 29

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.943

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

GnomAD4 genome AF: 0.938 AC: 142640 AN: 152004 Hom.: 66971 Cov.: 29 AF XY: 0.939 AC XY: 69711 AN XY: 74278

African (AFR) AF: 0.966 AC: 40013 AN: 41426

American (AMR) AF: 0.946 AC: 14459 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3168 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5136 AN: 5138

South Asian (SAS) AF: 0.937 AC: 4505 AN: 4810

European-Finnish (FIN) AF: 0.908 AC: 9596 AN: 10572

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62678 AN: 68002

Other (OTH) AF: 0.943 AC: 1986 AN: 2106

Alfa AF: 0.930 Hom.: 8509

Bravo AF: 0.942

Asia WGS AF: 0.973 AC: 3385 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	7.7
DANN	Benign	0.53
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1989756; hg19: chr8-16858690;