Genetic Variant FGF1:c.169+130G>T (chr5-142613829-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000800.5(FGF1):c.169+130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 960,512 control chromosomes in the GnomAD database, including 1,533 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 850 hom., cov: 33)

Exomes 𝑓: 0.016 ( 683 hom. )

Consequence

FGF1
NM_000800.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0720

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF1	NM_000800.5 link	c.169+130G>T		intron_variant	Intron 2 of 3	ENST00000337706.7	NP_000791.1	P05230-1A0A7U3JVZ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF1	ENST00000337706.7 link	c.169+130G>T		intron_variant	Intron 2 of 3	2	NM_000800.5	ENSP00000338548.2		P05230-1

Frequencies

GnomAD3 genomes

AF:

0.0645

AC:

9806

AN:

152128

Hom.:

847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0295

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.00484

Gnomad OTH

AF:

0.0444

GnomAD4 exome

AF:

0.0159

AC:

12824

AN:

808266

Hom.:

683

AF XY:

0.0155

AC XY:

6241

AN XY:

403936

show subpopulations

African (AFR)

AF:

0.197

AC:

3740

AN:

18960

American (AMR)

AF:

0.0210

AC:

396

AN:

18842

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

214

AN:

15308

East Asian (EAS)

AF:

0.112

AC:

3576

AN:

31858

South Asian (SAS)

AF:

0.0246

AC:

1153

AN:

46826

European-Finnish (FIN)

AF:

0.00329

AC:

146

AN:

44416

Middle Eastern (MID)

AF:

0.0329

AC:

AN:

2612

European-Non Finnish (NFE)

AF:

0.00401

AC:

2376

AN:

592222

Other (OTH)

AF:

0.0305

AC:

1137

AN:

37222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

551

1102

1653

2204

2755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

206

412

618

824

1030

<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:

0.0646

AC:

9831

AN:

152246

Hom.:

850

Cov.:

AF XY:

0.0637

AC XY:

4740

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.193

AC:

8009

AN:

41506

American (AMR)

AF:

0.0294

AC:

450

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3470

East Asian (EAS)

AF:

0.135

AC:

698

AN:

5182

South Asian (SAS)

AF:

0.0296

AC:

143

AN:

4828

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00485

AC:

330

AN:

68022

Other (OTH)

AF:

0.0440

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

407

814

1220

1627

2034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0164

Hom.:

Bravo

AF:

0.0722

Asia WGS

AF:

0.0900

AC:

314

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

(source)

DANN

Benign

0.64

PhyloP100

0.072

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over