chr8-16996388-T-A

Variant names:

• chr8-16996388-T-A
• rs11203822
• NM_019851.3:c.287-630A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019851.3(FGF20):​c.287-630A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,838 control chromosomes in the GnomAD database, including 11,332 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 0.36 (11332 hom., cov: 31)
• Consequence: FGF20 NM_019851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 1 publications found

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]

FGF20 Gene-Disease associations (from GenCC):

• bilateral renal agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal hypodysplasia/aplasia 2

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.287-630A>T		intron_variant	Intron 1 of 2	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.287-630A>T		intron_variant	Intron 1 of 2	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.94-3071A>T		intron_variant	Intron 1 of 1	5		ENSP00000428072.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55007 AN: 151720 Hom.: 11328 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.362 AC: 55016 AN: 151838 Hom.: 11332 Cov.: 31 AF XY: 0.369 AC XY: 27392 AN XY: 74182

African (AFR) AF: 0.149 AC: 6181 AN: 41372

American (AMR) AF: 0.435 AC: 6647 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1830 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2719 AN: 5126

South Asian (SAS) AF: 0.489 AC: 2357 AN: 4822

European-Finnish (FIN) AF: 0.467 AC: 4918 AN: 10534

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28878 AN: 67936

Other (OTH) AF: 0.402 AC: 849 AN: 2112

Alfa AF: 0.379 Hom.: 1462

Bravo AF: 0.352

Asia WGS AF: 0.483 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.64
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11203822; hg19: chr8-16853897;