chr8-16992301-A-G

Variant names:

• chr8-16992301-A-G
• rs10888125
• NM_019851.3:c.*771T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_019851.3(FGF20):​c.*771T>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 0.372 in 151,926 control chromosomes in the GnomAD database, including 11,972 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 0.37 (11972 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FGF20 NM_019851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.*771T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.*771T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_019851.3	ENSP00000180166.5

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56442 AN: 151812 Hom.: 11968 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.416

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.372 AC: 56453 AN: 151926 Hom.: 11972 Cov.: 32 AF XY: 0.378 AC XY: 28083 AN XY: 74266

African (AFR) AF: 0.149 AC: 6199 AN: 41520

American (AMR) AF: 0.445 AC: 6785 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3466

East Asian (EAS) AF: 0.508 AC: 2615 AN: 5152

South Asian (SAS) AF: 0.504 AC: 2426 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4895 AN: 10452

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.443 AC: 30105 AN: 67946

Other (OTH) AF: 0.410 AC: 865 AN: 2108

Alfa AF: 0.412 Hom.: 5153

Bravo AF: 0.361

Asia WGS AF: 0.484 AC: 1671 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		3.3
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: rs10888125; hg19: chr8-16849810;