rs4559013

Variant names:

• chr5-171424620-A-G
• rs4559013
• NM_003862.3:c.69+4177A>G

Variant summary

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

The NM_003862.3(FGF18):​c.69+4177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,060 control chromosomes in the GnomAD database, including 21,763 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 0.53 (21763 hom., cov: 32)
• Consequence: FGF18 NM_003862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 5 publications found

Genes affected

FGF18 (HGNC:3674): (fibroblast growth factor 18) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members 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. It has been shown in vitro that this protein is able to induce neurite outgrowth in PC12 cells. Studies of the similar proteins in mouse and chick suggested that this protein is a pleiotropic growth factor that stimulates proliferation in a number of tissues, most notably the liver and small intestine. Knockout studies of the similar gene in mice implied the role of this protein in regulating proliferation and differentiation of midline cerebellar structures. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF18	NM_003862.3	c.69+4177A>G		intron_variant	Intron 2 of 4	ENST00000274625.6	NP_003853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF18	ENST00000274625.6	c.69+4177A>G		intron_variant	Intron 2 of 4	1	NM_003862.3	ENSP00000274625.5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81122 AN: 151942 Hom.: 21726 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.534 AC: 81200 AN: 152060 Hom.: 21763 Cov.: 32 AF XY: 0.533 AC XY: 39638 AN XY: 74318

African (AFR) AF: 0.551 AC: 22845 AN: 41478

American (AMR) AF: 0.482 AC: 7363 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2819 AN: 5168

South Asian (SAS) AF: 0.581 AC: 2804 AN: 4824

European-Finnish (FIN) AF: 0.548 AC: 5792 AN: 10560

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35887 AN: 67962

Other (OTH) AF: 0.535 AC: 1129 AN: 2110

Alfa AF: 0.530 Hom.: 35800

Bravo AF: 0.526

Asia WGS AF: 0.548 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.45
PhyloP100		0.22
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: rs4559013; hg19: chr5-170851624;