rs1847340

chr3-192562297-G-A

Variant summary

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

The NM_004113.6(FGF12):c.13+164884C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 152,186 control chromosomes in the GnomAD database, including 1,412 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 0.083 (1412 hom., cov: 32)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.13+164884C>T		intron_variant		ENST00000445105.7
FGF12	NM_001377292.1	c.13+164884C>T		intron_variant
FGF12	NM_001377293.1	c.-60+165187C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.13+164884C>T		intron_variant		1	NM_004113.6	A1

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12548 AN: 152068 Hom.: 1401 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00862

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0828 AC: 12595 AN: 152186 Hom.: 1412 Cov.: 32 AF XY: 0.0806 AC XY: 5999 AN XY: 74418

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.0551

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.00863

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0584 Hom.: 149

Bravo AF: 0.0923

Asia WGS AF: 0.0490 AC: 171 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.62
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1847340; hg19: chr3-192280086;