ENST00000885509.1:c.-199A>G

Variant names:

• chr5-177086459-A-G
• rs641101
• ENST00000885509.1:c.-199A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000885509.1(FGFR4):​c.-199A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,770 control chromosomes in the GnomAD database, including 32,127 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 0.63 (32127 hom., cov: 29)
• Consequence: FGFR4 ENST00000885509.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000885509.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR4	ENST00000885509.1		c.-199A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000555568.1
	FGFR4	ENST00000885509.1		c.-199A>G		5_prime_UTR	Exon 1 of 18	ENSP00000555568.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96136 AN: 151652 Hom.: 32118 Cov.: 29

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.634 AC: 96181 AN: 151770 Hom.: 32127 Cov.: 29 AF XY: 0.642 AC XY: 47590 AN XY: 74156

African (AFR) AF: 0.418 AC: 17273 AN: 41362

American (AMR) AF: 0.712 AC: 10868 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2382 AN: 3470

East Asian (EAS) AF: 0.974 AC: 4987 AN: 5120

South Asian (SAS) AF: 0.860 AC: 4131 AN: 4806

European-Finnish (FIN) AF: 0.733 AC: 7733 AN: 10546

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46708 AN: 67898

Other (OTH) AF: 0.633 AC: 1328 AN: 2098

Alfa AF: 0.668 Hom.: 61558

Bravo AF: 0.620

Asia WGS AF: 0.846 AC: 2940 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.52
PhyloP100		-0.69
PromoterAI		-0.041	Neutral

Splicing

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

Other links and lift over

dbSNP: rs641101; hg19: chr5-176513460;