rs308443

Variant names:

• chr4-122854612-G-A
• rs308443
• NM_001361665.2:c.179-21709G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001361665.2(FGF2):​c.179-21709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,142 control chromosomes in the GnomAD database, including 1,736 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 0.099 (1736 hom., cov: 32)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.179-21709G>A		intron_variant	Intron 1 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.578-21709G>A		intron_variant	Intron 1 of 2		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2	c.179-21709G>A		intron_variant	Intron 1 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.578-21709G>A		intron_variant	Intron 1 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.179-21709G>A		intron_variant	Intron 1 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15109 AN: 152024 Hom.: 1737 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0865

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

GnomAD4 genome AF: 0.0994 AC: 15127 AN: 152142 Hom.: 1736 Cov.: 32 AF XY: 0.0969 AC XY: 7212 AN XY: 74412

African (AFR) AF: 0.279 AC: 11576 AN: 41450

American (AMR) AF: 0.0466 AC: 712 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3466

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5182

South Asian (SAS) AF: 0.0956 AC: 460 AN: 4810

European-Finnish (FIN) AF: 0.0109 AC: 116 AN: 10606

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0267 AC: 1819 AN: 68016

Other (OTH) AF: 0.0861 AC: 182 AN: 2114

Alfa AF: 0.0509 Hom.: 892

Bravo AF: 0.109

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs308443; hg19: chr4-123775767;