NM_004113.6:c.229-8773C>T

Variant names:

• chr3-192179429-G-A
• rs975121
• NM_004113.6:c.229-8773C>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.229-8773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,954 control chromosomes in the GnomAD database, including 33,681 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 0.64 (33681 hom., cov: 32)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004113.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF12	NM_004113.6	MANE Select	c.229-8773C>T		intron	N/A	NP_004104.3
	FGF12	NM_021032.5		c.415-8773C>T		intron	N/A	NP_066360.1
	FGF12	NM_001377293.1		c.157-8773C>T		intron	N/A	NP_001364222.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF12	ENST00000445105.7	TSL:1 MANE Select	c.229-8773C>T		intron	N/A	ENSP00000393686.1
	FGF12	ENST00000454309.7	TSL:1	c.415-8773C>T		intron	N/A	ENSP00000413496.2
	FGF12	ENST00000450716.5	TSL:5	c.229-8773C>T		intron	N/A	ENSP00000397635.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96593 AN: 151836 Hom.: 33621 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.636 AC: 96707 AN: 151954 Hom.: 33681 Cov.: 32 AF XY: 0.638 AC XY: 47406 AN XY: 74262

African (AFR) AF: 0.903 AC: 37455 AN: 41456

American (AMR) AF: 0.637 AC: 9743 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2020 AN: 3442

East Asian (EAS) AF: 0.953 AC: 4946 AN: 5188

South Asian (SAS) AF: 0.721 AC: 3478 AN: 4822

European-Finnish (FIN) AF: 0.448 AC: 4716 AN: 10538

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32370 AN: 67914

Other (OTH) AF: 0.613 AC: 1294 AN: 2110

Alfa AF: 0.533 Hom.: 94530

Bravo AF: 0.666

Asia WGS AF: 0.825 AC: 2864 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.8
DANN	Benign	0.30
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: rs975121; hg19: chr3-191897218;