4-122895552-T-G

Variant names:

• chr4-122895552-T-G
• rs6854081
• NM_001361665.2:c.*3156T>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.*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
• 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: Benign. The variant received -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.

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.*3156T>G		3_prime_UTR	Exon 3 of 3	NP_001348594.1
	NUDT6	NM_007083.5	MANE Select	c.553+2072A>C		intron	N/A	NP_009014.2
	FGF2	NM_002006.6		c.*3156T>G		3_prime_UTR	Exon 3 of 3	NP_001997.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.*3156T>G		3_prime_UTR	Exon 3 of 3	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.*3156T>G		3_prime_UTR	Exon 3 of 3	ENSP00000264498.4
	NUDT6	ENST00000304430.10	TSL:1 MANE Select	c.553+2072A>C		intron	N/A	ENSP00000306070.5

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

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

African (AFR) AF: 0.117 AC: 4857 AN: 41534

American (AMR) AF: 0.0827 AC: 1264 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0846 AC: 408 AN: 4820

European-Finnish (FIN) AF: 0.0989 AC: 1049 AN: 10602

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9311 AN: 68016

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.125 Hom.: 1567

Bravo AF: 0.117

Asia WGS AF: 0.0420 AC: 146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		0.87
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: rs6854081; hg19: chr4-123816707;