5-177089630-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_213647.3(FGFR4):c.28G>A(p.Val10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,613,302 control chromosomes in the GnomAD database, including 50,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3672 hom., cov: 32)

Exomes 𝑓: 0.24 ( 46556 hom. )

Consequence

FGFR4
NM_213647.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.547

Publications

102 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.772808E-4).

BP6

Variant 5-177089630-G-A is Benign according to our data. Variant chr5-177089630-G-A is described in ClinVar as [Benign]. Clinvar id is 1291710.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR4	NM_213647.3 link	c.28G>A	p.Val10Ile	missense_variant	Exon 2 of 18	ENST00000292408.9	NP_998812.1	P22455-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR4	ENST00000292408.9 link	c.28G>A	p.Val10Ile	missense_variant	Exon 2 of 18	1	NM_213647.3	ENSP00000292408.4		P22455-1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29302

AN:

151966

Hom.:

3672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.246

AC:

61443

AN:

249458

AF XY:

0.243

show subpopulations

Gnomad AFR exome

AF:

0.0509

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.243

AC:

355547

AN:

1461218

Hom.:

46556

Cov.:

AF XY:

0.242

AC XY:

175842

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.0446

AC:

1494

AN:

33476

American (AMR)

AF:

0.313

AC:

13978

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4141

AN:

26132

East Asian (EAS)

AF:

0.537

AC:

21298

AN:

39688

South Asian (SAS)

AF:

0.220

AC:

19006

AN:

86200

European-Finnish (FIN)

AF:

0.229

AC:

12220

AN:

53356

Middle Eastern (MID)

AF:

0.0957

AC:

552

AN:

5768

European-Non Finnish (NFE)

AF:

0.242

AC:

269091

AN:

1111674

Other (OTH)

AF:

0.228

AC:

13767

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

14114

28228

42341

56455

70569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.193

AC:

29307

AN:

152084

Hom.:

3672

Cov.:

AF XY:

0.198

AC XY:

14728

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0545

AC:

2265

AN:

41524

American (AMR)

AF:

0.257

AC:

3921

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

590

AN:

3472

East Asian (EAS)

AF:

0.519

AC:

2674

AN:

5156

South Asian (SAS)

AF:

0.236

AC:

1135

AN:

4814

European-Finnish (FIN)

AF:

0.230

AC:

2432

AN:

10572

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15651

AN:

67960

Other (OTH)

AF:

0.179

AC:

377

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1143

2286

3429

4572

5715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.218

Hom.:

14025

Bravo

AF:

0.192

TwinsUK

AF:

0.240

AC:

891

ALSPAC

AF:

0.249

AC:

961

ESP6500AA

AF:

0.0611

AC:

269

ESP6500EA

AF:

0.227

AC:

1952

ExAC

AF:

0.236

AC:

28653

Asia WGS

AF:

0.307

AC:

1071

AN:

3476

EpiCase

AF:

0.213

EpiControl

AF:

0.213

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FGFR4-related disorder

Benign:1

Aug 21, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

not provided

Benign:1

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24200957) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.80

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.28

T;T;.;.;T;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.39

.;T;T;T;T;T;T;T

MetaRNN

Benign

0.00028

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;.;.;.;N;.;.;N

PhyloP100

-0.55

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.16

N;N;N;N;N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.42

T;T;T;T;T;T;T;T

Sift4G

Benign

0.46

T;T;T;T;T;T;T;T

Polyphen

0.0

B;B;.;.;B;.;.;B

Vest4

0.065

MPC

0.22

ClinPred

0.0015

GERP RS

-2.2

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.015

gMVP

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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5-177089630-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over