4-122826931-C-T

Variant names:

• chr4-122826931-C-T
• rs1449683
• NM_001361665.2:c.-244C>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.-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
• Publications: 21 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	NM_001361665.2	MANE Select	c.-244C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001348594.1	D9ZGF5
	FGF2	NM_001361665.2	MANE Select	c.-244C>T		5_prime_UTR	Exon 1 of 3	NP_001348594.1	D9ZGF5
	FGF2	NM_002006.6		c.156C>T	p.Ser52Ser	synonymous	Exon 1 of 3	NP_001997.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.-244C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000494222.1	P09038-2
	FGF2	ENST00000608478.1	TSL:1	c.-244C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000477134.1	P09038-2
	FGF2	ENST00000264498.9	TSL:1	c.156C>T	p.Ser52Ser	synonymous	Exon 1 of 3	ENSP00000264498.4	P09038-4

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

GnomAD2 exomes AF: 0.122 AC: 14176 AN: 116152 AF XY: 0.114

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 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

African (AFR) AF: 0.252 AC: 7012 AN: 27876

American (AMR) AF: 0.189 AC: 6040 AN: 31916

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 1536 AN: 23210

East Asian (EAS) AF: 0.137 AC: 4109 AN: 30088

South Asian (SAS) AF: 0.126 AC: 9132 AN: 72488

European-Finnish (FIN) AF: 0.101 AC: 3592 AN: 35692

Middle Eastern (MID) AF: 0.0920 AC: 364 AN: 3958

European-Non Finnish (NFE) AF: 0.0905 AC: 94691 AN: 1046322

Other (OTH) AF: 0.111 AC: 6000 AN: 54180

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

African (AFR) AF: 0.258 AC: 10682 AN: 41432

American (AMR) AF: 0.147 AC: 2243 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.152 AC: 779 AN: 5118

South Asian (SAS) AF: 0.123 AC: 592 AN: 4816

European-Finnish (FIN) AF: 0.106 AC: 1106 AN: 10470

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0886 AC: 6004 AN: 67792

Other (OTH) AF: 0.137 AC: 288 AN: 2108

Alfa AF: 0.0989 Hom.: 1140

Bravo AF: 0.153

Asia WGS AF: 0.180 AC: 624 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		1.5
PromoterAI		-0.024	Neutral
Mutation Taster		=300/0	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: rs1449683; hg19: chr4-123748086; COSMIC: COSV52648389;