4-122843353-A-G

Position:

• chr4-122843353-A-G

Variant summary

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

The NM_001361665.2(FGF2):​c.178+16001A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,166 control chromosomes in the GnomAD database, including 6,980 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 0.26 (6980 hom., cov: 33)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.178+16001A>G		intron_variant		ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.577+16001A>G		intron_variant			NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2	c.178+16001A>G		intron_variant			NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.577+16001A>G		intron_variant		1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.178+16001A>G		intron_variant		1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38955 AN: 152048 Hom.: 6958 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.257 AC: 39031 AN: 152166 Hom.: 6980 Cov.: 33 AF XY: 0.256 AC XY: 19052 AN XY: 74390

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.252

Alfa AF: 0.184 Hom.: 2053

Bravo AF: 0.273

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.8
DANN	Benign	0.54

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: rs308428; hg19: chr4-123764508;