rs743682

Positions:

• chr4-1796125-G-A
• chr4-1796125-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000142.5(FGFR3):​c.109+2082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,112 control chromosomes in the GnomAD database, including 3,147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3147 hom., cov: 32)
• Consequence: FGFR3 NM_000142.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR3	NM_000142.5	c.109+2082G>A		intron_variant		ENST00000440486.8	NP_000133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR3	ENST00000440486.8	c.109+2082G>A		intron_variant		5	NM_000142.5	ENSP00000414914.2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25446 AN: 151992 Hom.: 3143 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0953

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25478 AN: 152112 Hom.: 3147 Cov.: 32 AF XY: 0.166 AC XY: 12312 AN XY: 74380

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0710

Gnomad4 SAS AF: 0.0813

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0953

Gnomad4 OTH AF: 0.152

Alfa AF: 0.108 Hom.: 1549

Bravo AF: 0.183

Asia WGS AF: 0.0820 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.80
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

Other links and lift over

dbSNP: rs743682; hg19: chr4-1797852;