rs308381

Variant names:

• chr4-122861950-G-A
• rs308381
• NM_001361665.2:c.179-14371G>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.179-14371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,228 control chromosomes in the GnomAD database, including 65,253 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 0.92 (65253 hom., cov: 31)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 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.179-14371G>A		intron	N/A	NP_001348594.1
	FGF2	NM_002006.6		c.578-14371G>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.179-14371G>A		intron	N/A	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.578-14371G>A		intron	N/A	ENSP00000264498.4
	FGF2	ENST00000608478.1	TSL:1	c.179-14371G>A		intron	N/A	ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140694 AN: 152110 Hom.: 65204 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.925 AC: 140800 AN: 152228 Hom.: 65253 Cov.: 31 AF XY: 0.923 AC XY: 68725 AN XY: 74432

African (AFR) AF: 0.892 AC: 37039 AN: 41512

American (AMR) AF: 0.855 AC: 13066 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3173 AN: 3470

East Asian (EAS) AF: 0.959 AC: 4977 AN: 5188

South Asian (SAS) AF: 0.911 AC: 4379 AN: 4808

European-Finnish (FIN) AF: 0.964 AC: 10227 AN: 10608

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64846 AN: 68034

Other (OTH) AF: 0.915 AC: 1937 AN: 2116

Alfa AF: 0.932 Hom.: 9551

Bravo AF: 0.916

Asia WGS AF: 0.944 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.36
PhyloP100		-1.5
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: rs308381; hg19: chr4-123783105;