11-69814431-C-G

Variant names:

• chr11-69814431-C-G
• rs11263591
• NM_005247.4:c.324+1889G>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.324+1889G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,120 control chromosomes in the GnomAD database, including 23,055 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 0.55 (23055 hom., cov: 29)
• Consequence: FGF3 NM_005247.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF3	NM_005247.4	c.324+1889G>C		intron_variant	Intron 2 of 2	ENST00000334134.4	NP_005238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF3	ENST00000334134.4	c.324+1889G>C		intron_variant	Intron 2 of 2	1	NM_005247.4	ENSP00000334122.2
FGF3	ENST00000646078.1	n.171+1889G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 82996 AN: 151002 Hom.: 23037 Cov.: 29

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.550 AC: 83066 AN: 151120 Hom.: 23055 Cov.: 29 AF XY: 0.551 AC XY: 40634 AN XY: 73762

African (AFR) AF: 0.576 AC: 23685 AN: 41088

American (AMR) AF: 0.413 AC: 6271 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3137 AN: 5068

South Asian (SAS) AF: 0.456 AC: 2177 AN: 4778

European-Finnish (FIN) AF: 0.658 AC: 6873 AN: 10448

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37141 AN: 67768

Other (OTH) AF: 0.522 AC: 1098 AN: 2104

Alfa AF: 0.553 Hom.: 2831

Bravo AF: 0.535

Asia WGS AF: 0.534 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.79
DANN	Benign	0.34
PhyloP100		-0.079
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: rs11263591; hg19: chr11-69629199;