rs3135898

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000142.5(FGFR3):c.1959+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,611,346 control chromosomes in the GnomAD database, including 571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 59 hom., cov: 34)

Exomes 𝑓: 0.020 ( 512 hom. )

Consequence

FGFR3
NM_000142.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

FGFR3 (HGNC:3690): (fibroblast growth factor receptor 3) This gene encodes a member of the fibroblast growth factor receptor (FGFR) family, with its amino acid sequence being highly conserved between members and among divergent species. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist 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 of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance. Mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia. [provided by RefSeq, Aug 2017]

FGFR3 links:

FGFR3 (HGNC:):

FGFR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-1806195-G-A is Benign according to our data. Variant chr4-1806195-G-A is described in ClinVar as [Benign]. Clinvar id is 255335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1806195-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR3	NM_000142.5 linkuse as main transcript	c.1959+22G>A		intron_variant		ENST00000440486.8	NP_000133.1	P22607-1Q0IJ44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR3	ENST00000440486.8 linkuse as main transcript	c.1959+22G>A		intron_variant		5	NM_000142.5	ENSP00000414914.2		P22607-1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2861

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0649

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0307

AC:

7603

AN:

248012

Hom.:

227

AF XY:

0.0301

AC XY:

4061

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.00347

Gnomad AMR exome

AF:

0.0949

Gnomad ASJ exome

AF:

0.0421

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.0486

Gnomad FIN exome

AF:

0.00945

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0266

GnomAD4 exome

AF:

0.0198

AC:

28862

AN:

1459020

Hom.:

512

Cov.:

AF XY:

0.0206

AC XY:

14959

AN XY:

725816

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.0909

Gnomad4 ASJ exome

AF:

0.0423

Gnomad4 EAS exome

AF:

0.000555

Gnomad4 SAS exome

AF:

0.0509

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.0155

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0188

AC:

2866

AN:

152326

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1503

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00438

Gnomad4 AMR

AF:

0.0653

Gnomad4 ASJ

AF:

0.0441

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0470

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0231

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.0

DANN

Benign

0.91

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over