Genetic Variant FGF12:c.13+98560C>T (chr3-192628621-G-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_004113.6(FGF12):c.13+98560C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 149,542 control chromosomes in the GnomAD database, including 14,950 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 0.44 ( 14950 hom., cov: 28)

Consequence

FGF12
NM_004113.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.322

Publications

2 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FGF12	NM_004113.6 link	c.13+98560C>T	intron_variant	Intron 2 of 5	ENST00000445105.7	NP_004104.3
FGF12	NM_001377293.1 link	c.-60+98863C>T	intron_variant	Intron 1 of 4		NP_001364222.1
FGF12	NM_001377292.1 link	c.13+98560C>T	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+98560C>T		intron_variant	Intron 2 of 5	1	NM_004113.6	ENSP00000393686.1		P61328-2

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

65558

AN:

149502

Hom.:

14950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.444

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.432

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

GnomAD4 genome

AF:

0.438

AC:

65549

AN:

149542

Hom.:

14950

Cov.:

AF XY:

0.436

AC XY:

31754

AN XY:

72880

show subpopulations

African (AFR)

AF:

0.345

AC:

14077

AN:

40774

American (AMR)

AF:

0.362

AC:

5410

AN:

14934

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1634

AN:

3456

East Asian (EAS)

AF:

0.533

AC:

2728

AN:

5114

South Asian (SAS)

AF:

0.405

AC:

1933

AN:

4768

European-Finnish (FIN)

AF:

0.476

AC:

4659

AN:

9796

Middle Eastern (MID)

AF:

0.435

AC:

121

AN:

278

European-Non Finnish (NFE)

AF:

0.498

AC:

33618

AN:

67448

Other (OTH)

AF:

0.432

AC:

894

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1802

3604

5405

7207

9009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.421

Hom.:

3206

Bravo

AF:

0.430

Asia WGS

AF:

0.405

AC:

1395

AN:

3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.31

PhyloP100

-0.32

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