rs2011077

Positions:

• chr5-177094455-C-T

Variant summary

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

The NM_213647.3(FGFR4):​c.1519+680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,996 control chromosomes in the GnomAD database, including 3,711 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 0.19 (3711 hom., cov: 32)
• Consequence: FGFR4 NM_213647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR4	NM_213647.3	c.1519+680C>T		intron_variant		ENST00000292408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR4	ENST00000292408.9	c.1519+680C>T		intron_variant		1	NM_213647.3	P2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29506 AN: 151878 Hom.: 3711 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29511 AN: 151996 Hom.: 3711 Cov.: 32 AF XY: 0.199 AC XY: 14811 AN XY: 74294

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.179

Alfa AF: 0.218 Hom.: 3802

Bravo AF: 0.193

Asia WGS AF: 0.308 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2011077; hg19: chr5-176521456;