Genetic Variant FGF12:c.13+85137G>C (chr3-192642044-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004113.6(FGF12):c.13+85137G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,056 control chromosomes in the GnomAD database, including 23,573 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 0.55 ( 23573 hom., cov: 33)

Consequence

FGF12
NM_004113.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.310

Publications

4 publications found

Variant links:

Genes affected

FGF12 (HGNC:3668): (fibroblast growth factor 12) 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 growth factor lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, this protein accumulated in the nucleus, but was not secreted. The specific function of this gene has not yet been determined. [provided by RefSeq, Dec 2019]

FGF12 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 47
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FGF12 links:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FGF12	NM_004113.6 link	c.13+85137G>C	intron_variant	Intron 2 of 5	ENST00000445105.7	NP_004104.3
FGF12	NM_001377293.1 link	c.-60+85440G>C	intron_variant	Intron 1 of 4		NP_001364222.1
FGF12	NM_001377292.1 link	c.13+85137G>C	intron_variant	Intron 2 of 4		NP_001364221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF12	ENST00000445105.7 link	c.13+85137G>C		intron_variant	Intron 2 of 5	1	NM_004113.6	ENSP00000393686.1

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

83989

AN:

151938

Hom.:

23561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.669

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.553

AC:

84034

AN:

152056

Hom.:

23573

Cov.:

AF XY:

0.554

AC XY:

41182

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.535

AC:

22190

AN:

41448

American (AMR)

AF:

0.454

AC:

6940

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

2116

AN:

3470

East Asian (EAS)

AF:

0.669

AC:

3452

AN:

5162

South Asian (SAS)

AF:

0.618

AC:

2978

AN:

4820

European-Finnish (FIN)

AF:

0.570

AC:

6023

AN:

10570

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.565

AC:

38418

AN:

67992

Other (OTH)

AF:

0.571

AC:

1200

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1955

3910

5866

7821

9776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.547

Hom.:

2754

Bravo

AF:

0.545

Asia WGS

AF:

0.596

AC:

2071

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.6

(source)

DANN

Benign

0.37

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over