chr4-122897116-A-T

Variant names:

• chr4-122897116-A-T
• rs1476215
• NM_001361665.2:c.*4720A>T

Variant summary

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

The NM_001361665.2(FGF2):​c.*4720A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,554 control chromosomes in the GnomAD database, including 63,452 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 0.91 (63283 hom., cov: 32)
  • Exomes 𝑓: 0.94 (169 hom.)
• Consequence: FGF2 NM_001361665.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.*4720A>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000644866.2	NP_001348594.1
NUDT6	NM_007083.5	c.553+508T>A		intron_variant	Intron 4 of 4	ENST00000304430.10	NP_009014.2
FGF2	NM_002006.6	c.*4720A>T		3_prime_UTR_variant	Exon 3 of 3		NP_001997.5
NUDT6	NM_198041.3	c.46+508T>A		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.*4720A>T		3_prime_UTR_variant	Exon 3 of 3		NM_001361665.2	ENSP00000494222.1
NUDT6	ENST00000304430.10	c.553+508T>A		intron_variant	Intron 4 of 4	1	NM_007083.5	ENSP00000306070.5

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138440 AN: 152058 Hom.: 63235 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.821

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.944 AC: 357 AN: 378 Hom.: 169 Cov.: 0 AF XY: 0.942 AC XY: 196 AN XY: 208

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.958

Gnomad4 SAS exome AF: 0.889

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.910 AC: 138548 AN: 152176 Hom.: 63283 Cov.: 32 AF XY: 0.909 AC XY: 67644 AN XY: 74404

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.951

Gnomad4 OTH AF: 0.905

Alfa AF: 0.924 Hom.: 8081

Bravo AF: 0.902

Asia WGS AF: 0.940 AC: 3244 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.4
DANN	Benign	0.72

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: rs1476215; hg19: chr4-123818271;