5-177090460-T-C

Variant names:

• chr5-177090460-T-C
• rs446382
• NM_213647.3:c.162T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_213647.3(FGFR4):​c.162T>C​(p.Arg54Arg) 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. R54R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FGFR4 NM_213647.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• Publications: 25 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.479 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR4	NM_213647.3	MANE Select	c.162T>C	p.Arg54Arg	synonymous	Exon 3 of 18	NP_998812.1	P22455-1
	FGFR4	NM_001354984.2		c.162T>C	p.Arg54Arg	synonymous	Exon 3 of 18	NP_001341913.1	P22455-1
	FGFR4	NM_002011.5		c.162T>C	p.Arg54Arg	synonymous	Exon 3 of 18	NP_002002.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR4	ENST00000292408.9	TSL:1 MANE Select	c.162T>C	p.Arg54Arg	synonymous	Exon 3 of 18	ENSP00000292408.4	P22455-1
	FGFR4	ENST00000502906.5	TSL:1	c.162T>C	p.Arg54Arg	synonymous	Exon 3 of 18	ENSP00000424960.1	P22455-1
	FGFR4	ENST00000393637.5	TSL:1	c.162T>C	p.Arg54Arg	synonymous	Exon 2 of 16	ENSP00000377254.1	P22455-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1450940 Hom.: 0 Cov.: 77 AF XY: 0.00 AC XY: 0 AN XY: 721476

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 85414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108334

Other (OTH) AF: 0.00 AC: 0 AN: 60094

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.1
DANN	Benign	0.51
PhyloP100		0.48

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: rs446382; hg19: chr5-176517461;