4-122843353-A-G

Variant names:

• chr4-122843353-A-G
• rs308428
• NM_001361665.2:c.178+16001A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	NM_001361665.2	MANE Select	c.178+16001A>G		intron	N/A	NP_001348594.1
	FGF2	NM_002006.6		c.577+16001A>G		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+16001A>G		intron	N/A	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.577+16001A>G		intron	N/A	ENSP00000264498.4
	FGF2	ENST00000608478.1	TSL:1	c.178+16001A>G		intron	N/A	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

African (AFR) AF: 0.500 AC: 20735 AN: 41484

American (AMR) AF: 0.228 AC: 3489 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 748 AN: 3472

East Asian (EAS) AF: 0.154 AC: 795 AN: 5174

South Asian (SAS) AF: 0.342 AC: 1654 AN: 4830

European-Finnish (FIN) AF: 0.126 AC: 1335 AN: 10590

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9558 AN: 67996

Other (OTH) AF: 0.252 AC: 533 AN: 2112

Alfa AF: 0.189 Hom.: 2991

Bravo AF: 0.273

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.8
DANN	Benign	0.54
PhyloP100		-0.27
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: rs308428; hg19: chr4-123764508;