rs12718379

Variant names:

• chr8-17002568-G-A
• rs12718379
• NM_019851.3:c.-536C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-17002568-G-A
• chr8-17002568-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_019851.3(FGF20):​c.-536C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,056 control chromosomes in the GnomAD database, including 15,591 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 0.43 (15591 hom., cov: 32)
• Consequence: FGF20 NM_019851.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.-536C>T		upstream_gene_variant		ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.-536C>T		upstream_gene_variant		1	NM_019851.3	ENSP00000180166.5

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65791 AN: 151938 Hom.: 15586 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.433 AC: 65808 AN: 152056 Hom.: 15591 Cov.: 32 AF XY: 0.437 AC XY: 32440 AN XY: 74300

African (AFR) AF: 0.219 AC: 9094 AN: 41510

American (AMR) AF: 0.503 AC: 7680 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1994 AN: 3464

East Asian (EAS) AF: 0.521 AC: 2681 AN: 5144

South Asian (SAS) AF: 0.544 AC: 2619 AN: 4816

European-Finnish (FIN) AF: 0.502 AC: 5298 AN: 10560

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34693 AN: 67972

Other (OTH) AF: 0.475 AC: 1000 AN: 2106

Alfa AF: 0.465 Hom.: 6092

Bravo AF: 0.424

Asia WGS AF: 0.519 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.73
PhyloP100		0.49
PromoterAI		-0.027	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12718379; hg19: chr8-16860077;