rs308441

Variant names:

• chr4-122852910-C-T
• rs308441
• NM_001361665.2:c.179-23411C>T

Variant summary

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

The NM_001361665.2(FGF2):​c.179-23411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,068 control chromosomes in the GnomAD database, including 10,445 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 0.32 (10445 hom., cov: 33)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.179-23411C>T		intron_variant	Intron 1 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.578-23411C>T		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.179-23411C>T		intron_variant	Intron 1 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.578-23411C>T		intron_variant	Intron 1 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.179-23411C>T		intron_variant	Intron 1 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48617 AN: 151950 Hom.: 10418 Cov.: 33

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.320 AC: 48696 AN: 152068 Hom.: 10445 Cov.: 33 AF XY: 0.320 AC XY: 23788 AN XY: 74310

African (AFR) AF: 0.614 AC: 25446 AN: 41446

American (AMR) AF: 0.300 AC: 4585 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3466

East Asian (EAS) AF: 0.0733 AC: 380 AN: 5186

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4816

European-Finnish (FIN) AF: 0.217 AC: 2291 AN: 10556

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13241 AN: 68006

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.236 Hom.: 8909

Bravo AF: 0.337

Asia WGS AF: 0.184 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.40
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs308441; hg19: chr4-123774065;