5-177092286-G-A

Position:

• chr5-177092286-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213647.3(FGFR4):​c.728-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,505,656 control chromosomes in the GnomAD database, including 494,444 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (53485 hom., cov: 31)
  • Exomes 𝑓: 0.81 (440959 hom.)
• Consequence: FGFR4 NM_213647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: 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
FGFR4	NM_213647.3	c.728-35G>A		intron_variant		ENST00000292408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR4	ENST00000292408.9	c.728-35G>A		intron_variant		1	NM_213647.3	P2

Frequencies

GnomAD3 genomes AF: 0.835 AC: 127007 AN: 152036 Hom.: 53419 Cov.: 31

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.809

GnomAD3 exomes AF: 0.842 AC: 148656 AN: 176506 Hom.: 63035 AF XY: 0.839 AC XY: 79282 AN XY: 94538

Gnomad AFR exome AF: 0.908

Gnomad AMR exome AF: 0.878

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.926

Gnomad FIN exome AF: 0.848

Gnomad NFE exome AF: 0.782

Gnomad OTH exome AF: 0.811

GnomAD4 exome AF: 0.805 AC: 1089962 AN: 1353502 Hom.: 440959 Cov.: 33 AF XY: 0.807 AC XY: 533977 AN XY: 661950

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.872

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.916

Gnomad4 FIN exome AF: 0.844

Gnomad4 NFE exome AF: 0.785

Gnomad4 OTH exome AF: 0.816

GnomAD4 genome AF: 0.836 AC: 127132 AN: 152154 Hom.: 53485 Cov.: 31 AF XY: 0.839 AC XY: 62451 AN XY: 74392

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.929

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.812

Alfa AF: 0.810 Hom.: 11195

Bravo AF: 0.835

Asia WGS AF: 0.958 AC: 3331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs393923; hg19: chr5-176519287;