rs11263587

Variant names:

• chr11-69812894-A-G
• rs11263587
• NM_005247.4:c.325-2194T>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.325-2194T>C 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 151,976 control chromosomes in the GnomAD database, including 18,822 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 (18822 hom., cov: 32)
• Consequence: FGF3 NM_005247.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF3	NM_005247.4	c.325-2194T>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.325-2194T>C		intron_variant	Intron 2 of 2	1	NM_005247.4	ENSP00000334122.2
FGF3	ENST00000646078.1	n.172-2194T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75048 AN: 151858 Hom.: 18813 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.619

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: 75090 AN: 151976 Hom.: 18822 Cov.: 32 AF XY: 0.495 AC XY: 36784 AN XY: 74284

African (AFR) AF: 0.469 AC: 19463 AN: 41458

American (AMR) AF: 0.375 AC: 5729 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1686 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3176 AN: 5138

South Asian (SAS) AF: 0.421 AC: 2034 AN: 4826

European-Finnish (FIN) AF: 0.612 AC: 6471 AN: 10570

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

European-Non Finnish (NFE) AF: 0.511 AC: 34732 AN: 67922

Other (OTH) AF: 0.469 AC: 990 AN: 2110

Alfa AF: 0.511 Hom.: 2547

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	-0.99
CADD	Benign	0.17
DANN	Benign	0.42
PhyloP100		-1.3
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: rs11263587; hg19: chr11-69627662;