4-1801509-C-T

Position:

chr4-1801509-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.588C>T(p.Arg196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,563,482 control chromosomes in the GnomAD database, including 395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 161 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 234 hom. )

Consequence

FGFR3
NM_000142.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.19

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=-0.76).

BP6

Variant 4-1801509-C-T is Benign according to our data. Variant chr4-1801509-C-T is described in ClinVar as [Benign]. Clinvar id is 197630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1801509-C-T is described in Lovd as [Benign]. Variant chr4-1801509-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0816 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.588C>T	p.Arg196=	synonymous_variant	5/18	ENST00000440486.8	NP_000133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR3	ENST00000440486.8 linkuse as main transcript	c.588C>T	p.Arg196=	synonymous_variant	5/18	5	NM_000142.5	ENSP00000414914	P4	P22607-1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4548

AN:

152208

Hom.:

160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0840

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00582

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0145

AC:

2393

AN:

164648

Hom.:

AF XY:

0.0141

AC XY:

1254

AN XY:

88770

show subpopulations

Gnomad AFR exome

AF:

0.0861

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0265

Gnomad EAS exome

AF:

0.0216

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.000383

Gnomad NFE exome

AF:

0.00656

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.00868

AC:

12252

AN:

1411156

Hom.:

234

Cov.:

AF XY:

0.00883

AC XY:

6161

AN XY:

697356

show subpopulations

Gnomad4 AFR exome

AF:

0.0862

Gnomad4 AMR exome

AF:

0.0115

Gnomad4 ASJ exome

AF:

0.0274

Gnomad4 EAS exome

AF:

0.0250

Gnomad4 SAS exome

AF:

0.0177

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.00444

Gnomad4 OTH exome

AF:

0.0156

GnomAD4 genome

AF:

0.0299

AC:

4552

AN:

152326

Hom.:

161

Cov.:

AF XY:

0.0287

AC XY:

2139

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0839

Gnomad4 AMR

AF:

0.0185

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.0249

Gnomad4 SAS

AF:

0.0161

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00581

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0334

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

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, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 09, 2015	- -
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	GeneDx	Sep 21, 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	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 07, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.9

DANN

Benign

0.85

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