5-177091783-C-G

Variant names:

• chr5-177091783-C-G
• rs452885
• NM_213647.3:c.702C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000292408.9(FGFR4):​c.702C>G​(p.Arg234Arg) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R234R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FGFR4 ENST00000292408.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 29 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000292408.9. 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
	FGFR4	NM_213647.3	MANE Select	c.702C>G	p.Arg234Arg	synonymous	Exon 6 of 18	NP_998812.1
	FGFR4	NM_001354984.2		c.702C>G	p.Arg234Arg	synonymous	Exon 6 of 18	NP_001341913.1
	FGFR4	NM_002011.5		c.702C>G	p.Arg234Arg	synonymous	Exon 6 of 18	NP_002002.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR4	ENST00000292408.9	TSL:1 MANE Select	c.702C>G	p.Arg234Arg	synonymous	Exon 6 of 18	ENSP00000292408.4
	FGFR4	ENST00000502906.5	TSL:1	c.702C>G	p.Arg234Arg	synonymous	Exon 6 of 18	ENSP00000424960.1
	FGFR4	ENST00000393637.5	TSL:1	c.702C>G	p.Arg234Arg	synonymous	Exon 5 of 16	ENSP00000377254.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.44
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.50		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.50		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs452885; hg19: chr5-176518784;