4-1801977-T-C

Position:

chr4-1801977-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.882T>C(p.Asn294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,612,450 control chromosomes in the GnomAD database, including 21,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3852 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18050 hom. )

Consequence

FGFR3
NM_000142.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.695

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=-0.79).

BP6

Variant 4-1801977-T-C is Benign according to our data. Variant chr4-1801977-T-C is described in ClinVar as [Benign]. Clinvar id is 255346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1801977-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.695 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 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.882T>C	p.Asn294=	synonymous_variant	7/18	ENST00000440486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR3	ENST00000440486.8 linkuse as main transcript	c.882T>C	p.Asn294=	synonymous_variant	7/18	5	NM_000142.5	P4	P22607-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30446

AN:

151954

Hom.:

3823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.0695

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.160

AC:

39814

AN:

248846

Hom.:

3816

AF XY:

0.160

AC XY:

21647

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.355

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.0457

Gnomad SAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.151

AC:

220041

AN:

1460376

Hom.:

18050

Cov.:

AF XY:

0.152

AC XY:

110627

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.362

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.0927

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.201

AC:

30525

AN:

152074

Hom.:

3852

Cov.:

AF XY:

0.198

AC XY:

14696

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.354

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.0697

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.169

Hom.:

1484

Bravo

AF:

0.209

Asia WGS

AF:

0.180

AC:

622

AN:

3478

EpiCase

AF:

0.155

EpiControl

AF:

0.154

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

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, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	GeneDx	Mar 29, 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:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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