rs2305181

Positions:

chr4-1801524-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000142.5(FGFR3):c.603T>C(p.Ile201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,574,210 control chromosomes in the GnomAD database, including 3,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 1958 hom., cov: 33)

Exomes 𝑓: 0.015 ( 1799 hom. )

Consequence

FGFR3
NM_000142.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 4-1801524-T-C is Benign according to our data. Variant chr4-1801524-T-C is described in ClinVar as [Benign]. Clinvar id is 197628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1801524-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR3	NM_000142.5 linkuse as main transcript	c.603T>C	p.Ile201=	synonymous_variant	5/18	ENST00000440486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR3	ENST00000440486.8 linkuse as main transcript	c.603T>C	p.Ile201=	synonymous_variant	5/18	5	NM_000142.5	P4	P22607-1

Frequencies

GnomAD3 genomes

AF:

0.0918

AC:

13976

AN:

152188

Hom.:

1942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.0252

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00676

Gnomad OTH

AF:

0.0735

GnomAD3 exomes

AF:

0.0277

AC:

5015

AN:

180956

Hom.:

480

AF XY:

0.0238

AC XY:

2340

AN XY:

98344

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0267

Gnomad EAS exome

AF:

0.0221

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.000424

Gnomad NFE exome

AF:

0.00710

Gnomad OTH exome

AF:

0.0241

GnomAD4 exome

AF:

0.0153

AC:

21800

AN:

1421906

Hom.:

1799

Cov.:

AF XY:

0.0147

AC XY:

10347

AN XY:

703728

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.0228

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.0251

Gnomad4 SAS exome

AF:

0.0182

Gnomad4 FIN exome

AF:

0.000714

Gnomad4 NFE exome

AF:

0.00493

Gnomad4 OTH exome

AF:

0.0322

GnomAD4 genome

AF:

0.0922

AC:

14040

AN:

152304

Hom.:

1958

Cov.:

AF XY:

0.0881

AC XY:

6562

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.0382

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00675

Gnomad4 OTH

AF:

0.0737

Alfa

AF:

0.0448

Hom.:

318

Bravo

AF:

0.104

Asia WGS

AF:

0.0610

AC:

211

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 28, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 27, 2016	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.43

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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