5-171440573-A-G

Variant names:

• chr5-171440573-A-G
• rs3934591
• NM_003862.3:c.250+4300A>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.250+4300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,886 control chromosomes in the GnomAD database, including 23,319 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 (23319 hom., cov: 31)
• Consequence: FGF18 NM_003862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF18	NM_003862.3	MANE Select	c.250+4300A>G		intron	N/A	NP_003853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF18	ENST00000274625.6	TSL:1 MANE Select	c.250+4300A>G		intron	N/A	ENSP00000274625.5

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83839 AN: 151768 Hom.: 23277 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.553 AC: 83927 AN: 151886 Hom.: 23319 Cov.: 31 AF XY: 0.549 AC XY: 40740 AN XY: 74216

African (AFR) AF: 0.605 AC: 25034 AN: 41412

American (AMR) AF: 0.502 AC: 7651 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1967 AN: 3466

East Asian (EAS) AF: 0.551 AC: 2840 AN: 5158

South Asian (SAS) AF: 0.591 AC: 2841 AN: 4804

European-Finnish (FIN) AF: 0.492 AC: 5187 AN: 10544

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36568 AN: 67934

Other (OTH) AF: 0.553 AC: 1166 AN: 2110

Alfa AF: 0.561 Hom.: 3527

Bravo AF: 0.552

Asia WGS AF: 0.545 AC: 1896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.36
PhyloP100		-0.62
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: rs3934591; hg19: chr5-170867577; COSMIC: COSV51125473;