ENST00000479147.6:n.216+4597T>C

Variant names:

• chr9-127799409-T-C
• rs12379987
• ENST00000479147.6:n.216+4597T>C

Variant summary

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

The ENST00000479147.6(FPGS):​n.216+4597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,028 control chromosomes in the GnomAD database, including 13,529 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 (13529 hom., cov: 32)
• Consequence: FPGS ENST00000479147.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 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+4597T>C		intron_variant	Intron 1 of 7	5
FPGS	ENST00000479375.6	n.131+4597T>C		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63309 AN: 151910 Hom.: 13524 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.417 AC: 63361 AN: 152028 Hom.: 13529 Cov.: 32 AF XY: 0.411 AC XY: 30539 AN XY: 74306

African (AFR) AF: 0.428 AC: 17724 AN: 41440

American (AMR) AF: 0.443 AC: 6758 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3470

East Asian (EAS) AF: 0.691 AC: 3572 AN: 5170

South Asian (SAS) AF: 0.344 AC: 1658 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3206 AN: 10576

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27620 AN: 67972

Other (OTH) AF: 0.428 AC: 903 AN: 2108

Alfa AF: 0.411 Hom.: 17019

Bravo AF: 0.433

Asia WGS AF: 0.480 AC: 1671 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.75
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs12379987; hg19: chr9-130561688; COSMIC: COSV64675352;