ENST00000450716.5:c.-131+10234A>T

Variant names:

• chr3-192757470-T-A
• rs9831045
• ENST00000450716.5:c.-131+10234A>T

Variant summary

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

The ENST00000450716.5(FGF12):​c.-131+10234A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,128 control chromosomes in the GnomAD database, including 35,842 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 0.68 (35842 hom., cov: 32)
• Consequence: FGF12 ENST00000450716.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450716.5. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF12	ENST00000450716.5	TSL:5	c.-131+10234A>T		intron	N/A	ENSP00000397635.1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102755 AN: 152010 Hom.: 35789 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.676 AC: 102873 AN: 152128 Hom.: 35842 Cov.: 32 AF XY: 0.673 AC XY: 50019 AN XY: 74358

African (AFR) AF: 0.852 AC: 35369 AN: 41526

American (AMR) AF: 0.681 AC: 10410 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2256 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2366 AN: 5166

South Asian (SAS) AF: 0.662 AC: 3198 AN: 4828

European-Finnish (FIN) AF: 0.552 AC: 5820 AN: 10542

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41113 AN: 68004

Other (OTH) AF: 0.675 AC: 1422 AN: 2108

Alfa AF: 0.649 Hom.: 4057

Bravo AF: 0.693

Asia WGS AF: 0.600 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.39
PhyloP100		-0.12
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: rs9831045; hg19: chr3-192475259;