rs4453795

Variant names:

• chr3-192376186-A-G
• rs4453795
• NM_004113.6:c.14-15648T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-192376186-A-G
• chr3-192376186-A-T

Variant summary

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

The NM_004113.6(FGF12):​c.14-15648T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,520 control chromosomes in the GnomAD database, including 16,212 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 0.46 (16212 hom., cov: 31)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF12	NM_004113.6	c.14-15648T>C		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.14-15648T>C		intron_variant	Intron 2 of 5	1	NM_004113.6	ENSP00000393686.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68914 AN: 151404 Hom.: 16203 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.455 AC: 68965 AN: 151520 Hom.: 16212 Cov.: 31 AF XY: 0.455 AC XY: 33641 AN XY: 74016

African (AFR) AF: 0.582 AC: 24059 AN: 41356

American (AMR) AF: 0.379 AC: 5776 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1537 AN: 3460

East Asian (EAS) AF: 0.392 AC: 2021 AN: 5156

South Asian (SAS) AF: 0.483 AC: 2324 AN: 4812

European-Finnish (FIN) AF: 0.441 AC: 4570 AN: 10364

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27308 AN: 67834

Other (OTH) AF: 0.441 AC: 926 AN: 2102

Alfa AF: 0.417 Hom.: 51957

Bravo AF: 0.455

Asia WGS AF: 0.391 AC: 1351 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.75
PhyloP100		-1.2
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: rs4453795; hg19: chr3-192093975;