8-16993369-T-G

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.391-52A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,501,800 control chromosomes in the GnomAD database, including 2,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (1073 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1639 hom.)
• Consequence: FGF20 NM_019851.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.487

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=-0.82).
• BP6: Variant 8-16993369-T-G is Benign according to our data. Variant chr8-16993369-T-G is described in ClinVar as [Benign]. Clinvar id is 1236757.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF20	NM_019851.3	c.391-52A>C		intron_variant		ENST00000180166.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF20	ENST00000180166.6	c.391-52A>C		intron_variant		1	NM_019851.3	P1
FGF20	ENST00000519941.1	c.95-52A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12961 AN: 152108 Hom.: 1070 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0776

GnomAD3 exomes AF: 0.0421 AC: 7996 AN: 189798 Hom.: 429 AF XY: 0.0376 AC XY: 3881 AN XY: 103288

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.0315

Gnomad ASJ exome AF: 0.0240

Gnomad EAS exome AF: 0.0000639

Gnomad SAS exome AF: 0.00823

Gnomad FIN exome AF: 0.0280

Gnomad NFE exome AF: 0.0352

Gnomad OTH exome AF: 0.0482

GnomAD4 exome AF: 0.0372 AC: 50206 AN: 1349574 Hom.: 1639 Cov.: 21 AF XY: 0.0359 AC XY: 23980 AN XY: 668238

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.0348

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.00976

Gnomad4 FIN exome AF: 0.0300

Gnomad4 NFE exome AF: 0.0352

Gnomad4 OTH exome AF: 0.0477

GnomAD4 genome AF: 0.0852 AC: 12974 AN: 152226 Hom.: 1073 Cov.: 32 AF XY: 0.0822 AC XY: 6120 AN XY: 74430

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.0564

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0519 Hom.: 185

Bravo AF: 0.0941

Asia WGS AF: 0.0130 AC: 45 AN: 3478

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 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.9
Dann	Benign	0.60

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: rs6991982; hg19: chr8-16850878;