11-69814622-G-A

Position:

• chr11-69814622-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FGF3	NM_005247.4	c.324+1698C>T		intron_variant		ENST00000334134.4	NP_005238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF3	ENST00000334134.4	c.324+1698C>T		intron_variant		1	NM_005247.4	ENSP00000334122	P1
FGF3	ENST00000646078.1	n.171+1698C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.469

Alfa AF: 0.510 Hom.: 3378

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11263592; hg19: chr11-69629390;