5-171436505-C-T

Position:

• chr5-171436505-C-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+232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,048 control chromosomes in the GnomAD database, including 21,268 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 (21268 hom., cov: 32)
• Consequence: FGF18 NM_003862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF18	NM_003862.3	c.250+232C>T		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+232C>T		intron_variant		1	NM_003862.3	ENSP00000274625	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80052 AN: 151928 Hom.: 21227 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.527 AC: 80141 AN: 152048 Hom.: 21268 Cov.: 32 AF XY: 0.525 AC XY: 38977 AN XY: 74300

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.530

Alfa AF: 0.512 Hom.: 34711

Bravo AF: 0.527

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.49

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: rs4076077; hg19: chr5-170863509;