rs11263592

Variant names:

• chr11-69814622-G-A
• rs11263592
• NM_005247.4:c.324+1698C>T

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+1698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,884 control chromosomes in the GnomAD database, including 18,813 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 0.49 (18813 hom., cov: 31)
• Consequence: FGF3 NM_005247.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF3	NM_005247.4	c.324+1698C>T		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+1698C>T		intron_variant	Intron 2 of 2	1	NM_005247.4	ENSP00000334122.2
FGF3	ENST00000646078.1	n.171+1698C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75000 AN: 151766 Hom.: 18804 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.494 AC: 75042 AN: 151884 Hom.: 18813 Cov.: 31 AF XY: 0.495 AC XY: 36761 AN XY: 74222

African (AFR) AF: 0.470 AC: 19434 AN: 41380

American (AMR) AF: 0.375 AC: 5724 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1691 AN: 3468

East Asian (EAS) AF: 0.616 AC: 3176 AN: 5154

South Asian (SAS) AF: 0.422 AC: 2032 AN: 4820

European-Finnish (FIN) AF: 0.612 AC: 6469 AN: 10570

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34718 AN: 67910

Other (OTH) AF: 0.469 AC: 989 AN: 2110

Alfa AF: 0.507 Hom.: 6705

Bravo AF: 0.478

Asia WGS AF: 0.509 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.43
PhyloP100		-0.020
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: rs11263592; hg19: chr11-69629390;