4-122852284-T-C

Variant names:

• chr4-122852284-T-C
• rs167428
• NM_001361665.2:c.179-24037T>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.179-24037T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,084 control chromosomes in the GnomAD database, including 17,168 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 0.41 (17168 hom., cov: 32)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 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.179-24037T>C		intron	N/A	NP_001348594.1	D9ZGF5
	FGF2	NM_002006.6		c.578-24037T>C		intron	N/A	NP_001997.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.179-24037T>C		intron	N/A	ENSP00000494222.1	P09038-2
	FGF2	ENST00000264498.9	TSL:1	c.578-24037T>C		intron	N/A	ENSP00000264498.4	P09038-4
	FGF2	ENST00000608478.1	TSL:1	c.179-24037T>C		intron	N/A	ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62834 AN: 151966 Hom.: 17136 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.414 AC: 62913 AN: 152084 Hom.: 17168 Cov.: 32 AF XY: 0.409 AC XY: 30381 AN XY: 74318

African (AFR) AF: 0.784 AC: 32536 AN: 41478

American (AMR) AF: 0.355 AC: 5417 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1025 AN: 3470

East Asian (EAS) AF: 0.0988 AC: 512 AN: 5182

South Asian (SAS) AF: 0.323 AC: 1553 AN: 4810

European-Finnish (FIN) AF: 0.238 AC: 2519 AN: 10564

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18360 AN: 67984

Other (OTH) AF: 0.368 AC: 777 AN: 2112

Alfa AF: 0.329 Hom.: 24548

Bravo AF: 0.435

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.73
PhyloP100		-0.28
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: rs167428; hg19: chr4-123773439;