Variant rs387598 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_213647.3(FGFR4):c.92-221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 703,502 control chromosomes in the GnomAD database, including 215,179 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 0.75 ( 42709 hom., cov: 30)

Exomes 𝑓: 0.79 ( 172470 hom. )

Consequence

FGFR4
NM_213647.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0730

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]

FGFR4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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	Protein	UniProt
FGFR4	NM_213647.3 linkuse as main transcript	c.92-221G>A		intron_variant		ENST00000292408.9	NP_998812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR4	ENST00000292408.9 linkuse as main transcript	c.92-221G>A		intron_variant		1	NM_213647.3	ENSP00000292408	P2	P22455-1

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

113111

AN:

151594

Hom.:

42650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.788

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.892

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.748

Gnomad OTH

AF:

0.743

GnomAD3 exomes

AF:

0.809

AC:

110024

AN:

135916

Hom.:

45067

AF XY:

0.813

AC XY:

59831

AN XY:

73598

show subpopulations

Gnomad AFR exome

AF:

0.648

Gnomad AMR exome

AF:

0.856

Gnomad ASJ exome

AF:

0.757

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.883

Gnomad FIN exome

AF:

0.808

Gnomad NFE exome

AF:

0.751

Gnomad OTH exome

AF:

0.779

GnomAD4 exome

AF:

0.787

AC:

434183

AN:

551790

Hom.:

172470

Cov.:

AF XY:

0.790

AC XY:

235848

AN XY:

298432

show subpopulations

Gnomad4 AFR exome

AF:

0.665

Gnomad4 AMR exome

AF:

0.850

Gnomad4 ASJ exome

AF:

0.757

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.878

Gnomad4 FIN exome

AF:

0.810

Gnomad4 NFE exome

AF:

0.750

Gnomad4 OTH exome

AF:

0.771

GnomAD4 genome

AF:

0.746

AC:

113231

AN:

151712

Hom.:

42709

Cov.:

AF XY:

0.753

AC XY:

55809

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.661

Gnomad4 AMR

AF:

0.788

Gnomad4 ASJ

AF:

0.767

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.893

Gnomad4 FIN

AF:

0.817

Gnomad4 NFE

AF:

0.748

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.744

Hom.:

9723

Bravo

AF:

0.739

Asia WGS

AF:

0.926

AC:

3222

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.88

DANN

Benign

0.57

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over