rs9850123

chr3-192324394-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004113.6(FGF12):c.228+10967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,012 control chromosomes in the GnomAD database, including 5,386 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 0.24 (5386 hom., cov: 32)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.228+10967A>G		intron_variant		ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.228+10967A>G		intron_variant		1	NM_004113.6	A1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35938 AN: 151894 Hom.: 5369 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.237 AC: 35997 AN: 152012 Hom.: 5386 Cov.: 32 AF XY: 0.239 AC XY: 17747 AN XY: 74302

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.208

Alfa AF: 0.157 Hom.: 4386

Bravo AF: 0.249

Asia WGS AF: 0.306 AC: 1063 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.015
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs9850123; hg19: chr3-192042183;