Variant 5-177096596-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_213647.3(FGFR4):c.2016-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,612,768 control chromosomes in the GnomAD database, including 446,184 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.71 ( 39349 hom., cov: 31)

Exomes 𝑓: 0.74 ( 406835 hom. )

Consequence

FGFR4
NM_213647.3 splice_region, intron

Scores

Splicing: ADA: 0.00001988

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.937

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-177096596-A-G is Benign according to our data. Variant chr5-177096596-A-G is described in ClinVar as [Benign]. Clinvar id is 3060830.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 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.2016-8A>G		splice_region_variant, intron_variant		ENST00000292408.9	NP_998812.1	P22455-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FGFR4	ENST00000292408.9 linkuse as main transcript	c.2016-8A>G	splice_region_variant, intron_variant	1	NM_213647.3	ENSP00000292408.4	P22455-1
FGFR4	ENST00000502906.5 linkuse as main transcript	c.2016-8A>G	splice_region_variant, intron_variant	1		ENSP00000424960.1	P22455-1
FGFR4	ENST00000393637.5 linkuse as main transcript	c.1896-8A>G	splice_region_variant, intron_variant	1		ENSP00000377254.1	P22455-2
FGFR4	ENST00000393648.6 linkuse as main transcript	c.1812-8A>G	splice_region_variant, intron_variant	2		ENSP00000377259.2	J3KPQ0

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108604

AN:

151870

Hom.:

39325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.626

Gnomad AMI

AF:

0.699

Gnomad AMR

AF:

0.755

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.900

Gnomad FIN

AF:

0.761

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.704

GnomAD3 exomes

AF:

0.771

AC:

193009

AN:

250256

Hom.:

75604

AF XY:

0.774

AC XY:

104681

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.844

Gnomad ASJ exome

AF:

0.704

Gnomad EAS exome

AF:

0.972

Gnomad SAS exome

AF:

0.893

Gnomad FIN exome

AF:

0.755

Gnomad NFE exome

AF:

0.716

Gnomad OTH exome

AF:

0.737

GnomAD4 exome

AF:

0.743

AC:

1085722

AN:

1460782

Hom.:

406835

Cov.:

AF XY:

0.747

AC XY:

542623

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.622

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.978

Gnomad4 SAS exome

AF:

0.888

Gnomad4 FIN exome

AF:

0.754

Gnomad4 NFE exome

AF:

0.724

Gnomad4 OTH exome

AF:

0.743

GnomAD4 genome

AF:

0.715

AC:

108667

AN:

151986

Hom.:

39349

Cov.:

AF XY:

0.721

AC XY:

53559

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.626

Gnomad4 AMR

AF:

0.756

Gnomad4 ASJ

AF:

0.711

Gnomad4 EAS

AF:

0.975

Gnomad4 SAS

AF:

0.901

Gnomad4 FIN

AF:

0.761

Gnomad4 NFE

AF:

0.722

Gnomad4 OTH

AF:

0.702

Alfa

AF:

0.715

Hom.:

25904

Bravo

AF:

0.707

Asia WGS

AF:

0.881

AC:

3064

AN:

3478

EpiCase

AF:

0.707

EpiControl

AF:

0.706

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FGFR4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over