rs7700205

Variant names:

• chr4-122877028-C-T
• rs7700205
• NM_001361665.2:c.282+604C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001361665.2(FGF2):​c.282+604C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,098 control chromosomes in the GnomAD database, including 1,610 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 0.14 (1610 hom., cov: 32)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.971
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.282+604C>T		intron_variant	Intron 2 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.681+604C>T		intron_variant	Intron 2 of 2		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2	c.282+604C>T		intron_variant	Intron 2 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.681+604C>T		intron_variant	Intron 2 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.282+604C>T		intron_variant	Intron 2 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21233 AN: 151982 Hom.: 1608 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.140 AC: 21255 AN: 152098 Hom.: 1610 Cov.: 32 AF XY: 0.135 AC XY: 10018 AN XY: 74352

African (AFR) AF: 0.125 AC: 5204 AN: 41494

American (AMR) AF: 0.101 AC: 1541 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5178

South Asian (SAS) AF: 0.0958 AC: 462 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1265 AN: 10548

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

European-Non Finnish (NFE) AF: 0.173 AC: 11731 AN: 67992

Other (OTH) AF: 0.144 AC: 304 AN: 2106

Alfa AF: 0.149 Hom.: 214

Bravo AF: 0.138

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		0.97
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: rs7700205; hg19: chr4-123798183;