rs9831045

Positions:

• chr3-192757470-T-A
• chr3-192757470-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF12	ENST00000450716.5	c.-131+10234A>T		intron_variant		5		ENSP00000397635	A1

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

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.675

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9831045; hg19: chr3-192475259;