8-16992623-A-T

Position:

• chr8-16992623-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019851.3(FGF20):​c.*449T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,650 control chromosomes in the GnomAD database, including 37,848 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 0.69 (37789 hom., cov: 30)
  • Exomes 𝑓: 0.68 (59 hom.)
• Consequence: FGF20 NM_019851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

Genes affected

FGF20 (HGNC:3677): (fibroblast growth factor 20) The protein encoded by this gene is a member of the fibroblast growth factor family. The fibroblast growth factors 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 product is a secreted neurotrophic factor but lacks a typical signal peptide. It is expressed in normal brain, particularly the cerebellum, and may regulate central nervous system development and function. Homodimerization of this protein was shown to regulate its receptor binding activity and concentration gradient in the extracellular matrix. Genetic variations of this gene have been associated with Parkinson disease susceptibility. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF20	NM_019851.3	c.*449T>A		3_prime_UTR_variant	3/3	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166	c.*449T>A		3_prime_UTR_variant	3/3	1	NM_019851.3	ENSP00000180166.5

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105126 AN: 151316 Hom.: 37774 Cov.: 30

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.702

GnomAD4 exome AF: 0.680 AC: 151 AN: 222 Hom.: 59 Cov.: 0 AF XY: 0.650 AC XY: 78 AN XY: 120

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.724

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.695 AC: 105177 AN: 151428 Hom.: 37789 Cov.: 30 AF XY: 0.699 AC XY: 51712 AN XY: 74006

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.699

Alfa AF: 0.741 Hom.: 5325

Bravo AF: 0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.53

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: rs1721082; hg19: chr8-16850132;