Menu
GeneBe

4-122827273-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001361665.2(FGF2):c.99C>T(p.Tyr33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00048 in 1,612,904 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00050 ( 3 hom. )

Consequence

FGF2
NM_001361665.2 synonymous

Scores

1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.26
Variant links:
Genes affected
FGF2 (HGNC:3676): (fibroblast growth factor 2) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-122827273-C-T is Benign according to our data. Variant chr4-122827273-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 740852.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.26 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGF2NM_001361665.2 linkuse as main transcriptc.99C>T p.Tyr33= synonymous_variant 1/3 ENST00000644866.2
FGF2NM_002006.6 linkuse as main transcriptc.498C>T p.Tyr166= synonymous_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGF2ENST00000644866.2 linkuse as main transcriptc.99C>T p.Tyr33= synonymous_variant 1/3 NM_001361665.2 P1P09038-2
FGF2ENST00000264498.9 linkuse as main transcriptc.498C>T p.Tyr166= synonymous_variant 1/31 P09038-4
FGF2ENST00000608478.1 linkuse as main transcriptc.99C>T p.Tyr33= synonymous_variant 1/31 P1P09038-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000243
AC:
37
AN:
152110
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000757
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000291
AC:
71
AN:
244150
Hom.:
0
AF XY:
0.000269
AC XY:
36
AN XY:
134046
show subpopulations
Gnomad AFR exome
AF:
0.0000685
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.000328
Gnomad NFE exome
AF:
0.000475
Gnomad OTH exome
AF:
0.000671
GnomAD4 exome
AF:
0.000505
AC:
737
AN:
1460676
Hom.:
3
Cov.:
33
AF XY:
0.000497
AC XY:
361
AN XY:
726670
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.000343
Gnomad4 NFE exome
AF:
0.000604
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000243
AC:
37
AN:
152228
Hom.:
0
Cov.:
31
AF XY:
0.000269
AC XY:
20
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000757
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000425
Hom.:
0
Bravo
AF:
0.000193
EpiCase
AF:
0.000545
EpiControl
AF:
0.000474

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeApr 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
12
Dann
Uncertain
0.98

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs113537066; hg19: chr4-123748428; API