rs12574452

chr11-69816963-G-Achr11-69816963-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005247.4(FGF3):c.221-540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,090 control chromosomes in the GnomAD database, including 8,184 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 0.32 (8184 hom., cov: 33)
• Consequence: FGF3 NM_005247.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

Genes affected

FGF3 (HGNC:3681): (fibroblast growth factor 3) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was identified by its similarity with mouse fgf3/int-2, a proto-oncogene activated in virally induced mammary tumors in the mouse. Frequent amplification of this gene has been found in human tumors, which may be important for neoplastic transformation and tumor progression. Studies of the similar genes in mouse and chicken suggested the role in inner ear formation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF3	NM_005247.4	c.221-540C>T		intron_variant		ENST00000334134.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF3	ENST00000334134.4	c.221-540C>T		intron_variant		1	NM_005247.4	P1
FGF3	ENST00000646078.1	n.67+521C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49356 AN: 151972 Hom.: 8184 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.325 AC: 49366 AN: 152090 Hom.: 8184 Cov.: 33 AF XY: 0.330 AC XY: 24499 AN XY: 74334

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.286

Alfa AF: 0.329 Hom.: 1085

Bravo AF: 0.310

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.50
Dann	Benign	0.35

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: rs12574452; hg19: chr11-69631731;