Variant 4-1803866-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000142.5(FGFR3):c.1075+30G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 1,605,042 control chromosomes in the GnomAD database, including 2,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 134 hom., cov: 34)

Exomes 𝑓: 0.051 ( 2113 hom. )

Consequence

FGFR3
NM_000142.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.21

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-1803866-G-C is Benign according to our data. Variant chr4-1803866-G-C is described in ClinVar as [Benign]. Clinvar id is 255322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1803866-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 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.1075+30G>C		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.1075+30G>C		intron_variant		5	NM_000142.5	ENSP00000414914.2		P22607-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5611

AN:

152200

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0371

AC:

9260

AN:

249742

Hom.:

248

AF XY:

0.0380

AC XY:

5149

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.00867

Gnomad AMR exome

AF:

0.0271

Gnomad ASJ exome

AF:

0.0696

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00925

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.0548

Gnomad OTH exome

AF:

0.0493

GnomAD4 exome

AF:

0.0505

AC:

73417

AN:

1452724

Hom.:

2113

Cov.:

AF XY:

0.0498

AC XY:

35994

AN XY:

723226

show subpopulations

Gnomad4 AFR exome

AF:

0.00894

Gnomad4 AMR exome

AF:

0.0285

Gnomad4 ASJ exome

AF:

0.0686

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00984

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.0581

Gnomad4 OTH exome

AF:

0.0474

GnomAD4 genome

AF:

0.0368

AC:

5609

AN:

152318

Hom.:

134

Cov.:

AF XY:

0.0348

AC XY:

2594

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.0395

Gnomad4 ASJ

AF:

0.0706

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00931

Gnomad4 FIN

AF:

0.0342

Gnomad4 NFE

AF:

0.0543

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0244

Hom.:

Bravo

AF:

0.0371

Asia WGS

AF:

0.00635

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	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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 24, 2018	- -
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

-0.82

CADD

Benign

7.3

DANN

Benign

0.51

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