NM_005247.4:c.325-1004T>C

Variant names:

• chr11-69811704-A-G
• rs1893047
• NM_005247.4:c.325-1004T>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.325-1004T>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 151,938 control chromosomes in the GnomAD database, including 23,228 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 (23228 hom., cov: 31)
• Consequence: FGF3 NM_005247.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 11 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF3	NM_005247.4	c.325-1004T>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.325-1004T>C		intron_variant	Intron 2 of 2	1	NM_005247.4	ENSP00000334122.2
FGF3	ENST00000646078.1	n.172-1004T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83508 AN: 151820 Hom.: 23210 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.550 AC: 83579 AN: 151938 Hom.: 23228 Cov.: 31 AF XY: 0.551 AC XY: 40915 AN XY: 74242

African (AFR) AF: 0.577 AC: 23920 AN: 41446

American (AMR) AF: 0.412 AC: 6299 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3472

East Asian (EAS) AF: 0.621 AC: 3170 AN: 5108

South Asian (SAS) AF: 0.457 AC: 2200 AN: 4810

European-Finnish (FIN) AF: 0.656 AC: 6925 AN: 10550

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37279 AN: 67950

Other (OTH) AF: 0.519 AC: 1096 AN: 2110

Alfa AF: 0.559 Hom.: 4297

Bravo AF: 0.536

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.56
PhyloP100		-1.5
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: rs1893047; hg19: chr11-69626472;