Variant rs2305183 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.616-40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,583,716 control chromosomes in the GnomAD database, including 23,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4667 hom., cov: 34)

Exomes 𝑓: 0.15 ( 18474 hom. )

Consequence

FGFR3
NM_000142.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.892

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=-0.93).

BP6

Variant 4-1801580-T-C is Benign according to our data. Variant chr4-1801580-T-C is described in ClinVar as [Benign]. Clinvar id is 255343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1801580-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 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.616-40T>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.616-40T>C		intron_variant		5	NM_000142.5	ENSP00000414914.2		P22607-1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32612

AN:

152088

Hom.:

4637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.0662

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.160

AC:

31080

AN:

193970

Hom.:

3100

AF XY:

0.160

AC XY:

16956

AN XY:

105956

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.0425

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.152

AC:

217972

AN:

1431510

Hom.:

18474

Cov.:

AF XY:

0.154

AC XY:

109056

AN XY:

709838

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.0942

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.215

AC:

32699

AN:

152206

Hom.:

4667

Cov.:

AF XY:

0.211

AC XY:

15722

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.0664

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.125

Hom.:

292

Bravo

AF:

0.226

Asia WGS

AF:

0.181

AC:

629

AN:

3476

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	Jun 14, 2018	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	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

-0.93

CADD

Benign

0.39

DANN

Benign

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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