4-122826931-C-T

Variant names:

• chr4-122826931-C-T
• rs1449683
• NM_001361665.2:c.-244C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001361665.2(FGF2):​c.-244C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,477,398 control chromosomes in the GnomAD database, including 9,558 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 0.15 (2061 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7497 hom.)
• Consequence: FGF2 NM_001361665.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.-244C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000644866.2	NP_001348594.1
FGF2	NM_001361665.2	c.-244C>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.156C>T	p.Ser52Ser	synonymous_variant	Exon 1 of 3		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866	c.-244C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000644866	c.-244C>T		5_prime_UTR_variant	Exon 1 of 3		NM_001361665.2	ENSP00000494222.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21933 AN: 151558 Hom.: 2045 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.122 AC: 14176 AN: 116152 Hom.: 1043 AF XY: 0.114 AC XY: 7540 AN XY: 66040

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.0630

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0863

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0999 AC: 132476 AN: 1325730 Hom.: 7497 Cov.: 33 AF XY: 0.0996 AC XY: 65065 AN XY: 653520

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0905

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.145 AC: 21999 AN: 151668 Hom.: 2061 Cov.: 32 AF XY: 0.145 AC XY: 10743 AN XY: 74138

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0886

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0886 Hom.: 696

Bravo AF: 0.153

Asia WGS AF: 0.180 AC: 624 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs1449683; hg19: chr4-123748086; COSMIC: COSV52648389;