8-16992907-A-G

Variant names:

• chr8-16992907-A-G
• rs2640901
• NM_019851.3:c.*165T>C

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.*165T>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 0.988 in 778,892 control chromosomes in the GnomAD database, including 380,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70168 hom., cov: 31)
  • Exomes 𝑓: 1.0 (310494 hom.)
• Consequence: FGF20 NM_019851.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.609
• Publications: 5 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=-0.89).
• BP6: Variant 8-16992907-A-G is Benign according to our data. Variant chr8-16992907-A-G is described in ClinVar as Benign. ClinVar VariationId is 1271718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019851.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF20	NM_019851.3	MANE Select	c.*165T>C		3_prime_UTR	Exon 3 of 3	NP_062825.1	Q9NP95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF20	ENST00000180166.6	TSL:1 MANE Select	c.*165T>C		3_prime_UTR	Exon 3 of 3	ENSP00000180166.5	Q9NP95
	FGF20	ENST00000519941.1	TSL:5	c.*165T>C		downstream_gene	N/A	ENSP00000428072.1	H0YAT9

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145686 AN: 152006 Hom.: 70116 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.972

GnomAD4 exome AF: 0.995 AC: 623701 AN: 626768 Hom.: 310494 Cov.: 8 AF XY: 0.996 AC XY: 322452 AN XY: 323810

African (AFR) AF: 0.849 AC: 13238 AN: 15594

American (AMR) AF: 0.990 AC: 18364 AN: 18542

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 14553 AN: 14554

East Asian (EAS) AF: 1.00 AC: 31589 AN: 31592

South Asian (SAS) AF: 1.00 AC: 48271 AN: 48284

European-Finnish (FIN) AF: 1.00 AC: 30226 AN: 30232

Middle Eastern (MID) AF: 0.995 AC: 3310 AN: 3328

European-Non Finnish (NFE) AF: 1.00 AC: 433069 AN: 433236

Other (OTH) AF: 0.990 AC: 31081 AN: 31406

GnomAD4 genome AF: 0.958 AC: 145797 AN: 152124 Hom.: 70168 Cov.: 31 AF XY: 0.960 AC XY: 71397 AN XY: 74396

African (AFR) AF: 0.854 AC: 35383 AN: 41432

American (AMR) AF: 0.988 AC: 15100 AN: 15282

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3468 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5167 AN: 5168

South Asian (SAS) AF: 0.999 AC: 4821 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10598 AN: 10598

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68003 AN: 68030

Other (OTH) AF: 0.973 AC: 2054 AN: 2112

Alfa AF: 0.984 Hom.: 14108

Bravo AF: 0.953

Asia WGS AF: 0.991 AC: 3445 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism

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: rs2640901; hg19: chr8-16850416;