NM_003862.3:c.548C>T

Variant names:

• chr5-171456729-C-T
• rs150911562
• NM_003862.3:c.548C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003862.3(FGF18):​c.548C>T​(p.Pro183Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00087 in 1,613,856 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (3 hom.)
• Consequence: FGF18 NM_003862.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042396337).
• BS2: High AC in GnomAd4 at 85 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF18	NM_003862.3	MANE Select	c.548C>T	p.Pro183Leu	missense	Exon 5 of 5	NP_003853.1	O76093

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF18	ENST00000274625.6	TSL:1 MANE Select	c.548C>T	p.Pro183Leu	missense	Exon 5 of 5	ENSP00000274625.5	O76093
	FGF18	ENST00000966519.1		c.542C>T	p.Pro181Leu	missense	Exon 5 of 5	ENSP00000636578.1

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000550 AC: 138 AN: 250762 AF XY: 0.000545

Gnomad AFR exome AF: 0.000373

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000902 AC: 1319 AN: 1461850 Hom.: 3 Cov.: 31 AF XY: 0.000850 AC XY: 618 AN XY: 727232

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86258

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53388

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00114 AC: 1264 AN: 1112000

Other (OTH) AF: 0.000381 AC: 23 AN: 60396

GnomAD4 genome AF: 0.000559 AC: 85 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.000566 AC XY: 42 AN XY: 74236

African (AFR) AF: 0.000290 AC: 12 AN: 41370

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000948 Hom.: 0

Bravo AF: 0.000574

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000544 AC: 66

EpiCase AF: 0.000763

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	0.083
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.11
Sift	Benign	0.64	T
Sift4G	Benign	0.46	T
Polyphen		0.61	P
Vest4		0.085
MVP		0.69
MPC		1.1
ClinPred		0.022	T
GERP RS		4.7
Varity_R		0.071
gMVP		0.56
Mutation Taster		=89/11	polymorphism

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: rs150911562; hg19: chr5-170883733; COSMIC: COSV99079025;