3-192144401-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004113.6(FGF12):c.428-275del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,072 control chromosomes in the GnomAD database, including 1,494 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1494 hom., cov: 30)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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 -10 ACMG points.

• BP6: Variant 3-192144401-AC-A is Benign according to our data. Variant chr3-192144401-AC-A is described in ClinVar as [Benign]. Clinvar id is 1257397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.428-275del		intron_variant		ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.428-275del		intron_variant		1	NM_004113.6	A1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20609 AN: 151954 Hom.: 1492 Cov.: 30

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.136 AC: 20625 AN: 152072 Hom.: 1494 Cov.: 30 AF XY: 0.136 AC XY: 10085 AN XY: 74340

Gnomad4 AFR AF: 0.0981

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.152

Alfa AF: 0.141 Hom.: 174

Bravo AF: 0.131

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

Mar 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs3841953; hg19: chr3-191862190;