8-16993428-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019851.3(FGF20):c.391-111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,124,344 control chromosomes in the GnomAD database, including 3,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (465 hom., cov: 32)
  • Exomes 𝑓: 0.076 (3302 hom.)
• Consequence: FGF20 NM_019851.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.110

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-16993428-G-T is Benign according to our data. Variant chr8-16993428-G-T is described in ClinVar as [Benign]. Clinvar id is 1284084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF20	NM_019851.3	c.391-111C>A		intron_variant		ENST00000180166.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF20	ENST00000180166.6	c.391-111C>A		intron_variant		1	NM_019851.3	P1
FGF20	ENST00000519941.1	c.95-111C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9372 AN: 151844 Hom.: 465 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0364

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.0757 AC: 73619 AN: 972388 Hom.: 3302 AF XY: 0.0750 AC XY: 36835 AN XY: 490922

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.0284

Gnomad4 ASJ exome AF: 0.0371

Gnomad4 EAS exome AF: 0.000678

Gnomad4 SAS exome AF: 0.0590

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.0818

Gnomad4 OTH exome AF: 0.0676

GnomAD4 genome AF: 0.0616 AC: 9367 AN: 151956 Hom.: 465 Cov.: 32 AF XY: 0.0651 AC XY: 4835 AN XY: 74256

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.0364

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0275 Hom.: 24

Bravo AF: 0.0480

Asia WGS AF: 0.0450 AC: 154 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.1
Dann	Benign	0.66

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: rs17515317; hg19: chr8-16850937;