4-122862039-T-C

Position:

• chr4-122862039-T-C

Variant summary

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

The NM_001361665.2(FGF2):​c.179-14282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,248 control chromosomes in the GnomAD database, including 1,443 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 0.13 (1443 hom., cov: 32)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

Genes affected

FGF2 (HGNC:3676): (fibroblast growth factor 2) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.179-14282T>C		intron_variant		ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.578-14282T>C		intron_variant			NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2	c.179-14282T>C		intron_variant			NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.578-14282T>C		intron_variant		1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.179-14282T>C		intron_variant		1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19778 AN: 152130 Hom.: 1444 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.130 AC: 19775 AN: 152248 Hom.: 1443 Cov.: 32 AF XY: 0.126 AC XY: 9380 AN XY: 74446

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.146

Alfa AF: 0.153 Hom.: 1054

Bravo AF: 0.129

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.75

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: rs308382; hg19: chr4-123783194;