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5-177091783-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_213647.3(FGFR4):c.702C>T(p.Arg234=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,613,994 control chromosomes in the GnomAD database, including 481,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.75 ( 42857 hom., cov: 33)
Exomes 𝑓: 0.77 ( 438633 hom. )

Consequence

FGFR4
NM_213647.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.204
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-177091783-C-T is Benign according to our data. Variant chr5-177091783-C-T is described in ClinVar as [Benign]. Clinvar id is 3060679.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.204 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGFR4NM_213647.3 linkuse as main transcriptc.702C>T p.Arg234= synonymous_variant 6/18 ENST00000292408.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGFR4ENST00000292408.9 linkuse as main transcriptc.702C>T p.Arg234= synonymous_variant 6/181 NM_213647.3 P2P22455-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.746
AC:
113479
AN:
152056
Hom.:
42798
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.661
Gnomad AMI
AF:
0.703
Gnomad AMR
AF:
0.788
Gnomad ASJ
AF:
0.766
Gnomad EAS
AF:
0.998
Gnomad SAS
AF:
0.893
Gnomad FIN
AF:
0.818
Gnomad MID
AF:
0.699
Gnomad NFE
AF:
0.748
Gnomad OTH
AF:
0.742
GnomAD3 exomes
AF:
0.801
AC:
201253
AN:
251390
Hom.:
81543
AF XY:
0.802
AC XY:
108941
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.652
Gnomad AMR exome
AF:
0.863
Gnomad ASJ exome
AF:
0.755
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
0.885
Gnomad FIN exome
AF:
0.813
Gnomad NFE exome
AF:
0.751
Gnomad OTH exome
AF:
0.778
GnomAD4 exome
AF:
0.772
AC:
1128966
AN:
1461820
Hom.:
438633
Cov.:
63
AF XY:
0.774
AC XY:
563147
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.661
Gnomad4 AMR exome
AF:
0.856
Gnomad4 ASJ exome
AF:
0.755
Gnomad4 EAS exome
AF:
0.999
Gnomad4 SAS exome
AF:
0.879
Gnomad4 FIN exome
AF:
0.811
Gnomad4 NFE exome
AF:
0.755
Gnomad4 OTH exome
AF:
0.776
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.747
AC:
113599
AN:
152174
Hom.:
42857
Cov.:
33
AF XY:
0.753
AC XY:
56027
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.661
Gnomad4 AMR
AF:
0.788
Gnomad4 ASJ
AF:
0.766
Gnomad4 EAS
AF:
0.998
Gnomad4 SAS
AF:
0.894
Gnomad4 FIN
AF:
0.818
Gnomad4 NFE
AF:
0.748
Gnomad4 OTH
AF:
0.746
Alfa
AF:
0.747
Hom.:
27651
Bravo
AF:
0.739
Asia WGS
AF:
0.926
AC:
3222
AN:
3478
EpiCase
AF:
0.733
EpiControl
AF:
0.740

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

FGFR4-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
11
Dann
Benign
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs452885; hg19: chr5-176518784; COSMIC: COSV52807660; COSMIC: COSV52807660; API