4-122897356-A-G

Variant names:

• chr4-122897356-A-G
• rs1476217
• NM_001361665.2:c.*4960A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001361665.2(FGF2):​c.*4960A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 407,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FGF2 NM_001361665.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 26 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]

NUDT6 (HGNC:8053): (nudix hydrolase 6) This gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.*4960A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000644866.2	NP_001348594.1
NUDT6	NM_007083.5	c.553+268T>C		intron_variant	Intron 4 of 4	ENST00000304430.10	NP_009014.2
FGF2	NM_002006.6	c.*4960A>G		3_prime_UTR_variant	Exon 3 of 3		NP_001997.5
NUDT6	NM_198041.3	c.46+268T>C		intron_variant	Intron 4 of 4		NP_932158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2	c.*4960A>G		3_prime_UTR_variant	Exon 3 of 3		NM_001361665.2	ENSP00000494222.1
NUDT6	ENST00000304430.10	c.553+268T>C		intron_variant	Intron 4 of 4	1	NM_007083.5	ENSP00000306070.5

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151872 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 3 AN: 255878 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134932

African (AFR) AF: 0.00 AC: 0 AN: 7094

American (AMR) AF: 0.00 AC: 0 AN: 8598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8232

East Asian (EAS) AF: 0.00 AC: 0 AN: 16012

South Asian (SAS) AF: 0.00 AC: 0 AN: 23510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1186

European-Non Finnish (NFE) AF: 0.0000188 AC: 3 AN: 159944

Other (OTH) AF: 0.00 AC: 0 AN: 15404

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151872 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74158

African (AFR) AF: 0.0000242 AC: 1 AN: 41342

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 2677

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.80
PhyloP100		0.13

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: rs1476217; hg19: chr4-123818511;