Variant chr4-1793606-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.-103+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 149,536 control chromosomes in the GnomAD database, including 1,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1680 hom., cov: 31)

Exomes 𝑓: 0.16 ( 10 hom. )

Consequence

FGFR3
NM_000142.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.508

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:

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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=-0.55).

BP6

Variant 4-1793606-C-T is Benign according to our data. Variant chr4-1793606-C-T is described in ClinVar as [Benign]. Clinvar id is 1251273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 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.-103+141C>T		intron_variant		ENST00000440486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR3	ENST00000440486.8 linkuse as main transcript	c.-103+141C>T		intron_variant		5	NM_000142.5	P4	P22607-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20421

AN:

148772

Hom.:

1679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0538

Gnomad AMI

AF:

0.0973

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.161

AC:

106

AN:

658

Hom.:

AF XY:

0.154

AC XY:

AN XY:

482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0625

Gnomad4 ASJ exome

AF:

0.300

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.137

AC:

20421

AN:

148878

Hom.:

1680

Cov.:

AF XY:

0.138

AC XY:

10051

AN XY:

72664

show subpopulations

Gnomad4 AFR

AF:

0.0538

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.0257

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.0788

Hom.:

107

Bravo

AF:

0.130

Asia WGS

AF:

0.110

AC:

352

AN:

3224

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

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