rs7694627

Variant names:

• chr4-122867340-T-C
• rs7694627
• NM_001361665.2:c.179-8981T>C

Variant summary

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

The NM_001361665.2(FGF2):​c.179-8981T>C 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 152,174 control chromosomes in the GnomAD database, including 1,612 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 (1612 hom., cov: 32)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• Publications: 15 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=-0.85).
• 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.179-8981T>C		intron_variant	Intron 1 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.578-8981T>C		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.179-8981T>C		intron_variant	Intron 1 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.578-8981T>C		intron_variant	Intron 1 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.179-8981T>C		intron_variant	Intron 1 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21235 AN: 152056 Hom.: 1610 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.140 AC: 21257 AN: 152174 Hom.: 1612 Cov.: 32 AF XY: 0.135 AC XY: 10021 AN XY: 74398

African (AFR) AF: 0.126 AC: 5213 AN: 41518

American (AMR) AF: 0.101 AC: 1543 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 564 AN: 3472

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5186

South Asian (SAS) AF: 0.0949 AC: 458 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1271 AN: 10590

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

European-Non Finnish (NFE) AF: 0.172 AC: 11722 AN: 67976

Other (OTH) AF: 0.143 AC: 302 AN: 2114

Alfa AF: 0.162 Hom.: 6657

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	-0.85
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		-0.66
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: rs7694627; hg19: chr4-123788495;