4-122865924-G-A

Variant names:

• chr4-122865924-G-A
• rs308388
• NM_001361665.2:c.179-10397G>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.179-10397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,986 control chromosomes in the GnomAD database, including 12,653 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 0.40 (12653 hom., cov: 33)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001361665.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	NM_001361665.2	MANE Select	c.179-10397G>A		intron	N/A	NP_001348594.1
	FGF2	NM_002006.6		c.578-10397G>A		intron	N/A	NP_001997.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.179-10397G>A		intron	N/A	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.578-10397G>A		intron	N/A	ENSP00000264498.4
	FGF2	ENST00000608478.1	TSL:1	c.179-10397G>A		intron	N/A	ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61126 AN: 151866 Hom.: 12645 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.403 AC: 61187 AN: 151986 Hom.: 12653 Cov.: 33 AF XY: 0.405 AC XY: 30127 AN XY: 74314

African (AFR) AF: 0.478 AC: 19782 AN: 41420

American (AMR) AF: 0.343 AC: 5240 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1451 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2370 AN: 5166

South Asian (SAS) AF: 0.614 AC: 2953 AN: 4810

European-Finnish (FIN) AF: 0.327 AC: 3458 AN: 10560

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24628 AN: 67962

Other (OTH) AF: 0.386 AC: 815 AN: 2114

Alfa AF: 0.375 Hom.: 18796

Bravo AF: 0.398

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.51
PhyloP100		-1.3
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: rs308388; hg19: chr4-123787079;