chr5-171421120-G-A

Position:

• chr5-171421120-G-A

Variant summary

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

The NM_003862.3(FGF18):​c.69+677G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,132 control chromosomes in the GnomAD database, including 22,768 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 0.55 (22768 hom., cov: 34)
• Consequence: FGF18 NM_003862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF18	NM_003862.3	c.69+677G>A		intron_variant		ENST00000274625.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF18	ENST00000274625.6	c.69+677G>A		intron_variant		1	NM_003862.3	P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83086 AN: 152016 Hom.: 22746 Cov.: 34

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.547 AC: 83145 AN: 152132 Hom.: 22768 Cov.: 34 AF XY: 0.545 AC XY: 40510 AN XY: 74364

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.561

Alfa AF: 0.482 Hom.: 1940

Bravo AF: 0.545

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.95

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: rs6887323; hg19: chr5-170848124;