3-192144411-G-C

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.428-284C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,946 control chromosomes in the GnomAD database, including 19,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (19218 hom., cov: 32)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85

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=-0.94).
• BP6: Variant 3-192144411-G-C is Benign according to our data. Variant chr3-192144411-G-C is described in ClinVar as [Benign]. Clinvar id is 1234896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.428-284C>G		intron_variant		ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.428-284C>G		intron_variant		1	NM_004113.6	A1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73378 AN: 151828 Hom.: 19212 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.483 AC: 73414 AN: 151946 Hom.: 19218 Cov.: 32 AF XY: 0.485 AC XY: 35999 AN XY: 74258

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.492

Alfa AF: 0.530 Hom.: 2752

Bravo AF: 0.456

Asia WGS AF: 0.428 AC: 1488 AN: 3476

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 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.26
Dann	Benign	0.43

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: rs12498120; hg19: chr3-191862200;