chr4-122850863-C-A

Variant names:

• chr4-122850863-C-A
• rs308435
• NM_001361665.2:c.178+23511C>A

Variant summary

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

The NM_002006.6(FGF2):​c.577+23511C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,010 control chromosomes in the GnomAD database, including 8,052 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 0.27 (8052 hom., cov: 32)
• Consequence: FGF2 NM_002006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002006.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	NM_001361665.2	MANE Select	c.178+23511C>A		intron	N/A	NP_001348594.1
	FGF2	NM_002006.6		c.577+23511C>A		intron	N/A	NP_001997.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.178+23511C>A		intron	N/A	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.577+23511C>A		intron	N/A	ENSP00000264498.4
	FGF2	ENST00000608478.1	TSL:1	c.178+23511C>A		intron	N/A	ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41026 AN: 151892 Hom.: 8037 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.270 AC: 41081 AN: 152010 Hom.: 8052 Cov.: 32 AF XY: 0.267 AC XY: 19808 AN XY: 74310

African (AFR) AF: 0.553 AC: 22883 AN: 41408

American (AMR) AF: 0.178 AC: 2716 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3470

East Asian (EAS) AF: 0.0202 AC: 105 AN: 5190

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1743 AN: 10566

Middle Eastern (MID) AF: 0.243 AC: 70 AN: 288

European-Non Finnish (NFE) AF: 0.159 AC: 10811 AN: 67962

Other (OTH) AF: 0.260 AC: 549 AN: 2112

Alfa AF: 0.197 Hom.: 13367

Bravo AF: 0.280

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.4
DANN	Benign	0.82
PhyloP100		-0.12
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: rs308435; hg19: chr4-123772018;