chr4-122882215-C-T

Variant names:

• chr4-122882215-C-T
• rs12506776
• NM_001361665.2:c.282+5791C>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.282+5791C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,098 control chromosomes in the GnomAD database, including 2,411 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 0.16 (2411 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 5 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]

ENSG00000273007 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 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.282+5791C>T		intron	N/A	NP_001348594.1
	FGF2	NM_002006.6		c.681+5791C>T		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.282+5791C>T		intron	N/A	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.681+5791C>T		intron	N/A	ENSP00000264498.4
	FGF2	ENST00000608478.1	TSL:1	c.282+5791C>T		intron	N/A	ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24068 AN: 151978 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.141

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.158 AC: 24079 AN: 152098 Hom.: 2411 Cov.: 32 AF XY: 0.168 AC XY: 12492 AN XY: 74350

African (AFR) AF: 0.0577 AC: 2396 AN: 41524

American (AMR) AF: 0.176 AC: 2681 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2326 AN: 5158

South Asian (SAS) AF: 0.366 AC: 1763 AN: 4812

European-Finnish (FIN) AF: 0.202 AC: 2142 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11530 AN: 67968

Other (OTH) AF: 0.144 AC: 303 AN: 2108

Alfa AF: 0.175 Hom.: 1402

Bravo AF: 0.145

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.38
PhyloP100		-1.3
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: rs12506776; hg19: chr4-123803370;