chr4-122895552-T-G

Position:

• chr4-122895552-T-G

Variant summary

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

The NM_001361665.2(FGF2):​c.*3156T>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 0.117 in 152,242 control chromosomes in the GnomAD database, including 1,139 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 0.12 (1139 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: FGF2 NM_001361665.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF2	NM_001361665.2	c.*3156T>G		3_prime_UTR_variant	3/3	ENST00000644866.2
NUDT6	NM_007083.5	c.553+2072A>C		intron_variant		ENST00000304430.10
FGF2	NM_002006.6	c.*3156T>G		3_prime_UTR_variant	3/3
NUDT6	NM_198041.3	c.46+2072A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF2	ENST00000644866.2	c.*3156T>G		3_prime_UTR_variant	3/3		NM_001361665.2	P1
NUDT6	ENST00000304430.10	c.553+2072A>C		intron_variant		1	NM_007083.5	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17822 AN: 152122 Hom.: 1138 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.117 AC: 17835 AN: 152242 Hom.: 1139 Cov.: 33 AF XY: 0.113 AC XY: 8418 AN XY: 74444

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0846

Gnomad4 FIN AF: 0.0989

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.123

Alfa AF: 0.127 Hom.: 1281

Bravo AF: 0.117

Asia WGS AF: 0.0420 AC: 146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.59

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: rs6854081; hg19: chr4-123816707;