rs31777

chr5-177096561-C-A

Variant summary

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

The NM_213647.3(FGFR4):c.2016-43C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,606,570 control chromosomes in the GnomAD database, including 519,089 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 0.79 (47922 hom., cov: 32)
  • Exomes 𝑓: 0.80 (471167 hom.)
• Consequence: FGFR4 NM_213647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-0.81).
• 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.2016-43C>A		intron_variant		ENST00000292408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR4	ENST00000292408.9	c.2016-43C>A		intron_variant		1	NM_213647.3	P2
FGFR4	ENST00000393637.5	c.1896-43C>A		intron_variant		1		A2
FGFR4	ENST00000502906.5	c.2016-43C>A		intron_variant		1		P2
FGFR4	ENST00000393648.6	c.1812-43C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120270 AN: 151924 Hom.: 47863 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.778

GnomAD3 exomes AF: 0.831 AC: 204066 AN: 245480 Hom.: 85503 AF XY: 0.832 AC XY: 110351 AN XY: 132632

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.879

Gnomad ASJ exome AF: 0.782

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.921

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.780

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.803 AC: 1167801 AN: 1454528 Hom.: 471167 Cov.: 39 AF XY: 0.805 AC XY: 582330 AN XY: 723344

Gnomad4 AFR exome AF: 0.753

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: 0.843

Gnomad4 NFE exome AF: 0.785

Gnomad4 OTH exome AF: 0.808

GnomAD4 genome AF: 0.792 AC: 120388 AN: 152042 Hom.: 47922 Cov.: 32 AF XY: 0.797 AC XY: 59236 AN XY: 74314

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.781

Alfa AF: 0.784 Hom.: 8592

Bravo AF: 0.784

Asia WGS AF: 0.950 AC: 3306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.8
Dann	Benign	0.50
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: rs31777; hg19: chr5-176523562; COSMIC: COSV99448718; COSMIC: COSV99448718;