chr4-1793812-GCTGCCTTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000142.5(FGFR3):​c.-102-18_-102-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00677 in 177,748 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 8 hom., cov: 32)
Exomes 𝑓: 0.011 ( 0 hom. )

Consequence

FGFR3
NM_000142.5 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.849
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 4-1793812-GCTGCCTTC-G is Benign according to our data. Variant chr4-1793812-GCTGCCTTC-G is described in ClinVar as [Benign]. Clinvar id is 1229898.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-1793812-GCTGCCTTC-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00595 (886/148874) while in subpopulation NFE AF= 0.00873 (581/66554). AF 95% confidence interval is 0.00814. There are 8 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FGFR3NM_000142.5 linkuse as main transcriptc.-102-18_-102-11del splice_polypyrimidine_tract_variant, intron_variant ENST00000440486.8 NP_000133.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FGFR3ENST00000440486.8 linkuse as main transcriptc.-102-18_-102-11del splice_polypyrimidine_tract_variant, intron_variant 5 NM_000142.5 ENSP00000414914 P4P22607-1

Frequencies

GnomAD3 genomes
AF:
0.00595
AC:
885
AN:
148766
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00168
Gnomad AMI
AF:
0.0165
Gnomad AMR
AF:
0.00593
Gnomad ASJ
AF:
0.0124
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00696
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00873
Gnomad OTH
AF:
0.00877
GnomAD4 exome
AF:
0.0110
AC:
317
AN:
28874
Hom.:
0
AF XY:
0.0112
AC XY:
175
AN XY:
15572
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00326
Gnomad4 ASJ exome
AF:
0.00957
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0101
Gnomad4 NFE exome
AF:
0.0125
Gnomad4 OTH exome
AF:
0.00875
GnomAD4 genome
AF:
0.00595
AC:
886
AN:
148874
Hom.:
8
Cov.:
32
AF XY:
0.00573
AC XY:
416
AN XY:
72582
show subpopulations
Gnomad4 AFR
AF:
0.00168
Gnomad4 AMR
AF:
0.00592
Gnomad4 ASJ
AF:
0.0124
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00696
Gnomad4 NFE
AF:
0.00873
Gnomad4 OTH
AF:
0.00868
Alfa
AF:
0.00778
Hom.:
2

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 13, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs1452696194; hg19: chr4-1795539; API