3-192170334-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004113.6(FGF12):c.427+124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 688,786 control chromosomes in the GnomAD database, including 81,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (26048 hom., cov: 27)
  • Exomes 𝑓: 0.44 (55757 hom.)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-192170334-C-G is Benign according to our data. Variant chr3-192170334-C-G is described in ClinVar as [Benign]. Clinvar id is 1234571.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.427+124G>C		intron_variant		ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.427+124G>C		intron_variant		1	NM_004113.6	A1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 81942 AN: 149534 Hom.: 25977 Cov.: 27

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.442 AC: 238510 AN: 539150 Hom.: 55757 AF XY: 0.449 AC XY: 127849 AN XY: 284996

Gnomad4 AFR exome AF: 0.885

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.548 AC: 82061 AN: 149636 Hom.: 26048 Cov.: 27 AF XY: 0.550 AC XY: 40103 AN XY: 72880

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.518

Alfa AF: 0.448 Hom.: 2127

Bravo AF: 0.571

Asia WGS AF: 0.671 AC: 2333 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.1
Dann	Benign	0.74

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: rs2046917; hg19: chr3-191888123; COSMIC: COSV53194703; COSMIC: COSV53194703;