rs308420

Variant names:

• chr4-122846788-G-A
• rs308420
• NM_001361665.2:c.178+19436G>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.178+19436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,230 control chromosomes in the GnomAD database, including 1,403 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 (1403 hom., cov: 33)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.178+19436G>A		intron_variant	Intron 1 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.577+19436G>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.178+19436G>A		intron_variant	Intron 1 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.577+19436G>A		intron_variant	Intron 1 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.178+19436G>A		intron_variant	Intron 1 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19119 AN: 152112 Hom.: 1395 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.126 AC: 19164 AN: 152230 Hom.: 1403 Cov.: 33 AF XY: 0.129 AC XY: 9592 AN XY: 74422

African (AFR) AF: 0.178 AC: 7416 AN: 41550

American (AMR) AF: 0.130 AC: 1991 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3468

East Asian (EAS) AF: 0.149 AC: 772 AN: 5176

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4824

European-Finnish (FIN) AF: 0.111 AC: 1175 AN: 10592

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6092 AN: 68000

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.101 Hom.: 1403

Bravo AF: 0.128

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.53
PhyloP100		0.44
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: rs308420; hg19: chr4-123767943;