rs12574452

Variant names:

• chr11-69816963-G-A
• rs12574452
• NM_005247.4:c.221-540C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-69816963-G-A
• chr11-69816963-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

FGF3 Gene-Disease associations (from GenCC):

• deafness with labyrinthine aplasia, microtia, and microdontia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FGF3	NM_005247.4	c.221-540C>T		intron_variant	Intron 1 of 2	ENST00000334134.4	NP_005238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF3	ENST00000334134.4	c.221-540C>T		intron_variant	Intron 1 of 2	1	NM_005247.4	ENSP00000334122.2
FGF3	ENST00000646078.1	n.67+521C>T		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.284 AC: 11782 AN: 41484

American (AMR) AF: 0.242 AC: 3709 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2128 AN: 5160

South Asian (SAS) AF: 0.275 AC: 1324 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4992 AN: 10570

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23444 AN: 67974

Other (OTH) AF: 0.286 AC: 605 AN: 2112

Alfa AF: 0.327 Hom.: 1108

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12574452; hg19: chr11-69631731;