Genetic Variant FGFR4:p.Val10Phe (chr5-177089630-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_213647.3(FGFR4):c.28G>T(p.Val10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V10I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

FGFR4
NM_213647.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.547

Publications

102 publications found

Variant links:

Genes affected

FGFR4 (HGNC:3691): (fibroblast growth factor receptor 4) The protein encoded by this gene is a tyrosine kinase and cell surface receptor for fibroblast growth factors. The encoded protein is involved in the regulation of several pathways, including cell proliferation, cell differentiation, cell migration, lipid metabolism, bile acid biosynthesis, vitamin D metabolism, glucose uptake, and phosphate homeostasis. This protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment, and a cytoplasmic tyrosine kinase domain. The extracellular portion interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. [provided by RefSeq, Aug 2017]

FGFR4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13897026).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FGFR4	NM_213647.3	MANE Select	c.28G>T	p.Val10Phe	missense	Exon 2 of 18	NP_998812.1
FGFR4	NM_001354984.2		c.28G>T	p.Val10Phe	missense	Exon 2 of 18	NP_001341913.1
FGFR4	NM_002011.5		c.28G>T	p.Val10Phe	missense	Exon 2 of 18	NP_002002.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FGFR4	ENST00000292408.9	TSL:1 MANE Select	c.28G>T	p.Val10Phe	missense	Exon 2 of 18	ENSP00000292408.4
FGFR4	ENST00000502906.5	TSL:1	c.28G>T	p.Val10Phe	missense	Exon 2 of 18	ENSP00000424960.1
FGFR4	ENST00000393637.5	TSL:1	c.28G>T	p.Val10Phe	missense	Exon 1 of 16	ENSP00000377254.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249458

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.22

CADD

Benign

2.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.41

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.49

M_CAP

Benign

0.058

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.14

PhyloP100

-0.55

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.40

Sift

Uncertain

0.012

Sift4G

Benign

0.58

Polyphen

0.12

Vest4

0.24

MutPred

0.33

Loss of stability (P = 0.0406)

MVP

0.71

MPC

0.36

ClinPred

0.10

GERP RS

-2.2

PromoterAI

0.098

Neutral

(source)

Varity_R

0.055

gMVP

0.56

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over