Variant 4-1804792-C-T 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.1267-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,548,494 control chromosomes in the GnomAD database, including 10,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 957 hom., cov: 34)

Exomes 𝑓: 0.12 ( 9841 hom. )

Consequence

FGFR3
NM_000142.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -6.49

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=-0.68).

BP6

Variant 4-1804792-C-T is Benign according to our data. Variant chr4-1804792-C-T is described in ClinVar as [Benign]. Clinvar id is 255328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1804792-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 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.1267-32C>T		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.1267-32C>T		intron_variant		5	NM_000142.5	ENSP00000414914.2		P22607-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16176

AN:

152198

Hom.:

958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0585

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.0604

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.121

AC:

18775

AN:

154938

Hom.:

1343

AF XY:

0.116

AC XY:

9461

AN XY:

81742

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.0528

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.115

AC:

160569

AN:

1396178

Hom.:

9841

Cov.:

AF XY:

0.113

AC XY:

78126

AN XY:

688682

show subpopulations

Gnomad4 AFR exome

AF:

0.0554

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.0538

Gnomad4 FIN exome

AF:

0.0997

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.106

AC:

16178

AN:

152316

Hom.:

957

Cov.:

AF XY:

0.107

AC XY:

7986

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0585

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.202

Gnomad4 SAS

AF:

0.0608

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.0730

Hom.:

120

Bravo

AF:

0.111

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0030

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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