Variant rs393923 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.863

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=-0.91).

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 linkuse as main transcript	c.728-35G>A		intron_variant		ENST00000292408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR4	ENST00000292408.9 linkuse as main transcript	c.728-35G>A		intron_variant		1	NM_213647.3	P2	P22455-1

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

127007

AN:

152036

Hom.:

53419

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.807

AC XY:

533977

AN XY:

661950

show subpopulations

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.:

AF XY:

0.839

AC XY:

62451

AN XY:

74392

show subpopulations

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

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