Variant 5-177090291-A-G 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.92-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,566,204 control chromosomes in the GnomAD database, including 505,568 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.79 ( 47991 hom., cov: 33)

Exomes 𝑓: 0.80 ( 457577 hom. )

Consequence

FGFR4
NM_213647.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719

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

This place is a probable branch point but likely benign (scored 0 / 10). 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 link	c.92-99A>G		intron_variant		ENST00000292408.9	NP_998812.1	P22455-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR4	ENST00000292408.9 link	c.92-99A>G		intron_variant		1	NM_213647.3	ENSP00000292408.4		P22455-1

Frequencies

GnomAD3 genomes

AF:

0.792

AC:

120405

AN:

152022

Hom.:

47932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.929

Gnomad FIN

AF:

0.849

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.778

GnomAD3 exomes

AF:

0.833

AC:

188883

AN:

226708

Hom.:

79274

AF XY:

0.833

AC XY:

104280

AN XY:

125148

show subpopulations

Gnomad AFR exome

AF:

0.748

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:

0.845

Gnomad NFE exome

AF:

0.781

Gnomad OTH exome

AF:

0.805

GnomAD4 exome

AF:

0.802

AC:

1134742

AN:

1414064

Hom.:

457577

Cov.:

AF XY:

0.805

AC XY:

567797

AN XY:

705606

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.872

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.916

Gnomad4 FIN exome

AF:

0.843

Gnomad4 NFE exome

AF:

0.784

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.792

AC:

120523

AN:

152140

Hom.:

47991

Cov.:

AF XY:

0.797

AC XY:

59309

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.751

Gnomad4 AMR

AF:

0.812

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.929

Gnomad4 FIN

AF:

0.849

Gnomad4 NFE

AF:

0.780

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.791

Hom.:

21588

Bravo

AF:

0.785

Asia WGS

AF:

0.951

AC:

3308

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

0.16

DANN

Benign

0.41

BranchPoint Hunter

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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