rs9859577

Variant names:

• chr3-192370736-G-T
• rs9859577
• NM_004113.6:c.14-10198C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004113.6(FGF12):​c.14-10198C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,032 control chromosomes in the GnomAD database, including 5,333 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 0.24 (5333 hom., cov: 32)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 4 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF12	NM_004113.6	c.14-10198C>A		intron_variant	Intron 2 of 5	ENST00000445105.7	NP_004104.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF12	ENST00000445105.7	c.14-10198C>A		intron_variant	Intron 2 of 5	1	NM_004113.6	ENSP00000393686.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36552 AN: 151914 Hom.: 5315 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0899

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.241 AC: 36623 AN: 152032 Hom.: 5333 Cov.: 32 AF XY: 0.237 AC XY: 17629 AN XY: 74314

African (AFR) AF: 0.412 AC: 17057 AN: 41430

American (AMR) AF: 0.231 AC: 3518 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1282 AN: 5162

South Asian (SAS) AF: 0.271 AC: 1307 AN: 4816

European-Finnish (FIN) AF: 0.0899 AC: 952 AN: 10590

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11123 AN: 67986

Other (OTH) AF: 0.249 AC: 526 AN: 2112

Alfa AF: 0.194 Hom.: 4173

Bravo AF: 0.259

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.058
DANN	Benign	0.54
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9859577; hg19: chr3-192088525;