9-127798788-C-T

Variant names:

• chr9-127798788-C-T
• rs7033913
• ENST00000479147.6:n.216+3976C>T

Variant summary

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

The ENST00000479147.6(FPGS):​n.216+3976C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,134 control chromosomes in the GnomAD database, including 34,427 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 0.66 (34427 hom., cov: 33)
• Consequence: FPGS ENST00000479147.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

Genes affected

FPGS (HGNC:3824): (folylpolyglutamate synthase) This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of glutamate moieties to folate and folate derivatives. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000479147.6	n.216+3976C>T		intron_variant	Intron 1 of 7	5
FPGS	ENST00000479375.6	n.131+3976C>T		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99764 AN: 152016 Hom.: 34381 Cov.: 33

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99863 AN: 152134 Hom.: 34427 Cov.: 33 AF XY: 0.654 AC XY: 48628 AN XY: 74372

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.631

Alfa AF: 0.638 Hom.: 6251

Bravo AF: 0.673

Asia WGS AF: 0.815 AC: 2835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7033913; hg19: chr9-130561067;