dbSNP rs17223632: FGF1:p.Gly21Glu (chr5-142614066-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000800.5(FGF1):c.62G>A(p.Gly21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,614,152 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 31 hom. )

Consequence

FGF1
NM_000800.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.07

Publications

15 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007540971).

BP6

Variant 5-142614066-C-T is Benign according to our data. Variant chr5-142614066-C-T is described in ClinVar as Benign. ClinVar VariationId is 786817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00399 (5833/1461876) while in subpopulation MID AF = 0.0182 (105/5766). AF 95% confidence interval is 0.0154. There are 31 homozygotes in GnomAdExome4. There are 3161 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 529 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF1	NM_000800.5	MANE Select	c.62G>A	p.Gly21Glu	missense	Exon 2 of 4	NP_000791.1	P05230-1
FGF1	NM_001144892.3		c.62G>A	p.Gly21Glu	missense	Exon 2 of 4	NP_001138364.1	P05230-1
FGF1	NM_001144934.2		c.62G>A	p.Gly21Glu	missense	Exon 3 of 5	NP_001138406.1	P05230-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF1	ENST00000337706.7	TSL:2 MANE Select	c.62G>A	p.Gly21Glu	missense	Exon 2 of 4	ENSP00000338548.2	P05230-1
FGF1	ENST00000359370.10	TSL:1	c.62G>A	p.Gly21Glu	missense	Exon 2 of 4	ENSP00000352329.6	P05230-1
FGF1	ENST00000612258.4	TSL:1	c.62G>A	p.Gly21Glu	missense	Exon 3 of 5	ENSP00000479024.1	P05230-1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

530

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00404

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00452

AC:

1136

AN:

251470

AF XY:

0.00522

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00734

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00399

AC:

5833

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

3161

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33480

American (AMR)

AF:

0.00275

AC:

123

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00945

AC:

247

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0110

AC:

953

AN:

86256

European-Finnish (FIN)

AF:

0.00195

AC:

104

AN:

53420

Middle Eastern (MID)

AF:

0.0182

AC:

105

AN:

5766

European-Non Finnish (NFE)

AF:

0.00358

AC:

3982

AN:

1111998

Other (OTH)

AF:

0.00495

AC:

299

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

303

605

908

1210

1513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152276

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41544

American (AMR)

AF:

0.00699

AC:

107

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0108

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00404

AC:

275

AN:

68028

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00417

Hom.:

Bravo

AF:

0.00349

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00442

AC:

537

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00616

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0075

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

2.1

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.3

REVEL

Benign

0.037

Sift

Benign

0.066

Sift4G

Benign

0.42

Polyphen

0.066

Vest4

0.17

MVP

0.49

MPC

0.25

ClinPred

0.0082

GERP RS

1.9

Varity_R

0.19

gMVP

0.70

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over