4-1799784-C-T

Position:

chr4-1799784-C-T

Variant summary

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

The NM_000142.5(FGFR3):c.417C>T(p.Asp139=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,612,894 control chromosomes in the GnomAD database, including 1,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 131 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1606 hom. )

Consequence

FGFR3
NM_000142.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.28

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=-0.61).

BP6

Variant 4-1799784-C-T is Benign according to our data. Variant chr4-1799784-C-T is described in ClinVar as [Benign]. Clinvar id is 255340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1799784-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0686 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.417C>T	p.Asp139=	synonymous_variant	4/18	ENST00000440486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR3	ENST00000440486.8 linkuse as main transcript	c.417C>T	p.Asp139=	synonymous_variant	4/18	5	NM_000142.5	P4	P22607-1

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5466

AN:

152172

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00927

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.0829

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0408

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0495

Gnomad OTH

AF:

0.0417

GnomAD3 exomes

AF:

0.0396

AC:

9885

AN:

249744

Hom.:

283

AF XY:

0.0423

AC XY:

5730

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.00746

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.0855

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.0512

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0537

GnomAD4 exome

AF:

0.0441

AC:

64470

AN:

1460604

Hom.:

1606

Cov.:

AF XY:

0.0451

AC XY:

32759

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.00708

Gnomad4 AMR exome

AF:

0.0241

Gnomad4 ASJ exome

AF:

0.0861

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0481

Gnomad4 FIN exome

AF:

0.0485

Gnomad4 NFE exome

AF:

0.0459

Gnomad4 OTH exome

AF:

0.0463

GnomAD4 genome

AF:

0.0358

AC:

5458

AN:

152290

Hom.:

131

Cov.:

AF XY:

0.0358

AC XY:

2668

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00924

Gnomad4 AMR

AF:

0.0378

Gnomad4 ASJ

AF:

0.0829

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.0495

Gnomad4 OTH

AF:

0.0398

Alfa

AF:

0.0453

Hom.:

117

Bravo

AF:

0.0336

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.6

DANN

Benign

0.81

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