Variant chr5-142614088-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000800.5(FGF1):c.40G>C(p.Glu14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FGF1
NM_000800.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Variant links:

Genes affected

FGF1 (HGNC:3665): (fibroblast growth factor 1) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members 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 protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

FGF1 links:

SPRY4-AS1 (HGNC:53465): (SPRY4 antisense RNA 1)

SPRY4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF1	NM_000800.5 linkuse as main transcript	c.40G>C	p.Glu14Gln	missense_variant	2/4	ENST00000337706.7	NP_000791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF1	ENST00000337706.7 linkuse as main transcript	c.40G>C	p.Glu14Gln	missense_variant	2/4	2	NM_000800.5	ENSP00000338548	P1	P05230-1
SPRY4-AS1	ENST00000443800.5 linkuse as main transcript	n.356+32174C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251458

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.40G>C (p.E14Q) alteration is located in exon 3 (coding exon 1) of the FGF1 gene. This alteration results from a G to C substitution at nucleotide position 40, causing the glutamic acid (E) at amino acid position 14 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T;T;T;T;T;T;.;T;T;T;.;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

.;.;.;D;.;.;.;D;D;.;.;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.1

M;M;M;M;M;M;M;M;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.60

N;.;.;.;.;N;N;N;N;N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.075

T;.;.;.;.;T;T;D;D;T;T;D;D

Sift4G

Benign

0.10

T;T;T;T;T;T;T;T;T;T;T;.;D

Polyphen

0.97

D;D;D;D;D;D;D;D;.;D;D;.;.

Vest4

0.56

MutPred

0.46

Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);Loss of ubiquitination at K15 (P = 0.0353);

MVP

0.71

MPC

0.68

ClinPred

0.81

GERP RS

5.8

Varity_R

0.41

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over