rs11938826

Variant names:

• chr4-122851459-C-G
• rs11938826
• NM_001361665.2:c.178+24107C>G

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+24107C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,088 control chromosomes in the GnomAD database, including 11,272 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 0.30 (11272 hom., cov: 32)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 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.178+24107C>G		intron	N/A	NP_001348594.1
	FGF2	NM_002006.6		c.577+24107C>G		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.178+24107C>G		intron	N/A	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.577+24107C>G		intron	N/A	ENSP00000264498.4
	FGF2	ENST00000608478.1	TSL:1	c.178+24107C>G		intron	N/A	ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46275 AN: 151970 Hom.: 11226 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.305 AC: 46375 AN: 152088 Hom.: 11272 Cov.: 32 AF XY: 0.299 AC XY: 22249 AN XY: 74344

African (AFR) AF: 0.679 AC: 28160 AN: 41462

American (AMR) AF: 0.222 AC: 3390 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3466

East Asian (EAS) AF: 0.135 AC: 698 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1060 AN: 4814

European-Finnish (FIN) AF: 0.108 AC: 1147 AN: 10590

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10658 AN: 67984

Other (OTH) AF: 0.271 AC: 573 AN: 2114

Alfa AF: 0.238 Hom.: 971

Bravo AF: 0.332

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.59
DANN	Benign	0.40
PhyloP100		0.0060
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: rs11938826; hg19: chr4-123772614;