rs9313543

Variant names:

• chr5-171427385-G-A
• rs9313543
• NM_003862.3:c.69+6942G>A

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+6942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,110 control chromosomes in the GnomAD database, including 2,527 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 0.18 (2527 hom., cov: 32)
• Consequence: FGF18 NM_003862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF18	NM_003862.3	c.69+6942G>A		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+6942G>A		intron_variant	Intron 2 of 4	1	NM_003862.3	ENSP00000274625.5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26952 AN: 151990 Hom.: 2523 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.177 AC: 26965 AN: 152110 Hom.: 2527 Cov.: 32 AF XY: 0.178 AC XY: 13266 AN XY: 74360

African (AFR) AF: 0.149 AC: 6162 AN: 41494

American (AMR) AF: 0.108 AC: 1657 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3472

East Asian (EAS) AF: 0.261 AC: 1349 AN: 5162

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4816

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13064 AN: 67982

Other (OTH) AF: 0.184 AC: 387 AN: 2106

Alfa AF: 0.185 Hom.: 5338

Bravo AF: 0.164

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.76
PhyloP100		-0.24
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: rs9313543; hg19: chr5-170854389;