NM_001361665.2:c.*4960A>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001361665.2(FGF2):​c.*4960A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 406,886 control chromosomes in the GnomAD database, including 35,738 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 0.42 (14021 hom., cov: 32)
  • Exomes 𝑓: 0.40 (21717 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.596 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.*4960A>C		3_prime_UTR	Exon 3 of 3	NP_001348594.1
	NUDT6	NM_007083.5	MANE Select	c.553+268T>G		intron	N/A	NP_009014.2
	FGF2	NM_002006.6		c.*4960A>C		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.*4960A>C		3_prime_UTR	Exon 3 of 3	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.*4960A>C		3_prime_UTR	Exon 3 of 3	ENSP00000264498.4
	NUDT6	ENST00000304430.10	TSL:1 MANE Select	c.553+268T>G		intron	N/A	ENSP00000306070.5

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63857 AN: 151828 Hom.: 14003 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.399 AC: 101779 AN: 254940 Hom.: 21717 Cov.: 0 AF XY: 0.411 AC XY: 55201 AN XY: 134448

African (AFR) AF: 0.548 AC: 3874 AN: 7068

American (AMR) AF: 0.330 AC: 2826 AN: 8566

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 3369 AN: 8202

East Asian (EAS) AF: 0.486 AC: 7748 AN: 15950

South Asian (SAS) AF: 0.615 AC: 14415 AN: 23446

European-Finnish (FIN) AF: 0.322 AC: 5102 AN: 15848

Middle Eastern (MID) AF: 0.468 AC: 554 AN: 1184

European-Non Finnish (NFE) AF: 0.364 AC: 57971 AN: 159326

Other (OTH) AF: 0.386 AC: 5920 AN: 15350

GnomAD4 genome AF: 0.421 AC: 63931 AN: 151946 Hom.: 14021 Cov.: 32 AF XY: 0.423 AC XY: 31436 AN XY: 74260

African (AFR) AF: 0.539 AC: 22333 AN: 41448

American (AMR) AF: 0.349 AC: 5330 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2404 AN: 5172

South Asian (SAS) AF: 0.615 AC: 2963 AN: 4820

European-Finnish (FIN) AF: 0.327 AC: 3455 AN: 10550

Middle Eastern (MID) AF: 0.486 AC: 141 AN: 290

European-Non Finnish (NFE) AF: 0.363 AC: 24644 AN: 67894

Other (OTH) AF: 0.399 AC: 843 AN: 2114

Alfa AF: 0.343 Hom.: 2677

Bravo AF: 0.419

Asia WGS AF: 0.505 AC: 1748 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		0.13
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: rs1476217; hg19: chr4-123818511;