rs1960669

Variant names:

• chr4-122861413-C-A
• rs1960669
• NM_001361665.2:c.179-14908C>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.179-14908C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,146 control chromosomes in the GnomAD database, including 1,430 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 (1430 hom., cov: 31)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 14 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 (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.179-14908C>A		intron_variant	Intron 1 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.578-14908C>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.179-14908C>A		intron_variant	Intron 1 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.578-14908C>A		intron_variant	Intron 1 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.179-14908C>A		intron_variant	Intron 1 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19697 AN: 152028 Hom.: 1430 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.130 AC: 19713 AN: 152146 Hom.: 1430 Cov.: 31 AF XY: 0.127 AC XY: 9434 AN XY: 74392

African (AFR) AF: 0.156 AC: 6469 AN: 41506

American (AMR) AF: 0.0724 AC: 1107 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5182

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4820

European-Finnish (FIN) AF: 0.171 AC: 1809 AN: 10578

Middle Eastern (MID) AF: 0.121 AC: 35 AN: 290

European-Non Finnish (NFE) AF: 0.138 AC: 9408 AN: 67988

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.130 Hom.: 2210

Bravo AF: 0.124

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.49
PhyloP100		-0.76
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: rs1960669; hg19: chr4-123782568;