rs4073716

Positions:

• chr5-171437235-A-G
• chr5-171437235-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003862.3(FGF18):​c.250+962A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,056 control chromosomes in the GnomAD database, including 21,923 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 (21923 hom., cov: 33)
• Consequence: FGF18 NM_003862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF18	NM_003862.3	c.250+962A>G		intron_variant		ENST00000274625.6	NP_003853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF18	ENST00000274625.6	c.250+962A>G		intron_variant		1	NM_003862.3	ENSP00000274625	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81211 AN: 151938 Hom.: 21881 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.535 AC: 81301 AN: 152056 Hom.: 21923 Cov.: 33 AF XY: 0.532 AC XY: 39531 AN XY: 74314

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.538

Alfa AF: 0.519 Hom.: 9320

Bravo AF: 0.534

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.8
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs4073716; hg19: chr5-170864239;