rs1721100

Variant names:

• chr8-16992989-C-G
• rs1721100
• NM_019851.3:c.*83G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 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 -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 VariationId 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 rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.*83G>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.*83G>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.*83G>C		3_prime_UTR_variant	Exon 2 of 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

African (AFR) AF: 0.481 AC: 14282 AN: 29692

American (AMR) AF: 0.640 AC: 20792 AN: 32476

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 17212 AN: 21312

East Asian (EAS) AF: 0.478 AC: 18525 AN: 38726

South Asian (SAS) AF: 0.670 AC: 47800 AN: 71330

European-Finnish (FIN) AF: 0.701 AC: 31355 AN: 44758

Middle Eastern (MID) AF: 0.755 AC: 4005 AN: 5308

European-Non Finnish (NFE) AF: 0.707 AC: 730353 AN: 1032906

Other (OTH) AF: 0.697 AC: 38693 AN: 55490

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

African (AFR) AF: 0.488 AC: 20217 AN: 41412

American (AMR) AF: 0.645 AC: 9821 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2776 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2631 AN: 5154

South Asian (SAS) AF: 0.658 AC: 3161 AN: 4802

European-Finnish (FIN) AF: 0.690 AC: 7270 AN: 10540

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48321 AN: 67976

Other (OTH) AF: 0.655 AC: 1384 AN: 2112

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.3
DANN	Benign	0.51
PhyloP100		0.95
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: rs1721100; hg19: chr8-16850498; COSMIC: COSV51661310;