rs3804158

Variant names:

• chr4-122893745-G-A
• rs3804158
• NM_001361665.2:c.*1349G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001361665.2(FGF2):​c.*1349G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,096 control chromosomes in the GnomAD database, including 15,851 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 (15846 hom., cov: 33)
  • Exomes 𝑓: 0.44 (5 hom.)
• Consequence: FGF2 NM_001361665.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.*1349G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000644866.2	NP_001348594.1
NUDT6	NM_007083.5	c.554-520C>T		intron_variant	Intron 4 of 4	ENST00000304430.10	NP_009014.2
FGF2	NM_002006.6	c.*1349G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001997.5
NUDT6	NM_198041.3	c.47-520C>T		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.*1349G>A		3_prime_UTR_variant	Exon 3 of 3		NM_001361665.2	ENSP00000494222.1
NUDT6	ENST00000304430.10	c.554-520C>T		intron_variant	Intron 4 of 4	1	NM_007083.5	ENSP00000306070.5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62737 AN: 151942 Hom.: 15840 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.444 AC: 16 AN: 36 Hom.: 5 Cov.: 0 AF XY: 0.563 AC XY: 9 AN XY: 16

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.413 AC: 62747 AN: 152060 Hom.: 15846 Cov.: 33 AF XY: 0.410 AC XY: 30484 AN XY: 74308

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.441

Alfa AF: 0.521 Hom.: 27894

Bravo AF: 0.397

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs3804158; hg19: chr4-123814900;