NM_004113.6:c.13+74937C>T

Variant names:

• chr3-192652244-G-A
• rs3898006
• NM_004113.6:c.13+74937C>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.13+74937C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,060 control chromosomes in the GnomAD database, including 25,175 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 0.57 (25175 hom., cov: 33)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 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.13+74937C>T		intron	N/A	NP_004104.3
	FGF12	NM_001377293.1		c.-60+75240C>T		intron	N/A	NP_001364222.1
	FGF12	NM_001377292.1		c.13+74937C>T		intron	N/A	NP_001364221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF12	ENST00000445105.7	TSL:1 MANE Select	c.13+74937C>T		intron	N/A	ENSP00000393686.1
	FGF12	ENST00000450716.5	TSL:5	c.13+74937C>T		intron	N/A	ENSP00000397635.1
	FGF12	ENST00000683451.2		c.13+74937C>T		intron	N/A	ENSP00000508366.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86733 AN: 151942 Hom.: 25165 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.571 AC: 86772 AN: 152060 Hom.: 25175 Cov.: 33 AF XY: 0.571 AC XY: 42469 AN XY: 74352

African (AFR) AF: 0.540 AC: 22411 AN: 41472

American (AMR) AF: 0.471 AC: 7188 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2121 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3446 AN: 5156

South Asian (SAS) AF: 0.637 AC: 3066 AN: 4816

European-Finnish (FIN) AF: 0.593 AC: 6279 AN: 10592

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40302 AN: 67970

Other (OTH) AF: 0.585 AC: 1235 AN: 2110

Alfa AF: 0.591 Hom.: 13628

Bravo AF: 0.560

Asia WGS AF: 0.610 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.26
PhyloP100		-0.070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3898006; hg19: chr3-192370033;