rs1721100

Positions:

• chr8-16992989-C-G
• chr8-16992989-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019851.3(FGF20):​c.*83G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,483,902 control chromosomes in the GnomAD database, including 353,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31514 hom., cov: 31)
  • Exomes 𝑓: 0.69 (322145 hom.)
• Consequence: FGF20 NM_019851.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.947

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-16992989-C-G is Benign according to our data. Variant chr8-16992989-C-G is described in ClinVar as [Benign]. Clinvar id is 1289305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF20	NM_019851.3	c.*83G>C		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.*83G>C		3_prime_UTR_variant	3/3	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.*83G>C		3_prime_UTR_variant	2/2	5		ENSP00000428072.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96460 AN: 151786 Hom.: 31496 Cov.: 31

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.693 AC: 923017 AN: 1331998 Hom.: 322145 Cov.: 19 AF XY: 0.693 AC XY: 456957 AN XY: 658990

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.640

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.701

Gnomad4 NFE exome AF: 0.707

Gnomad4 OTH exome AF: 0.697

GnomAD4 genome AF: 0.635 AC: 96516 AN: 151904 Hom.: 31514 Cov.: 31 AF XY: 0.636 AC XY: 47177 AN XY: 74224

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.655

Alfa AF: 0.673 Hom.: 4202

Bravo AF: 0.627

Asia WGS AF: 0.568 AC: 1977 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.3
DANN	Benign	0.51

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: rs1721100; hg19: chr8-16850498; COSMIC: COSV51661310;