ENST00000479147.6:n.216+135G>A

Variant names:

• chr9-127794947-G-A
• rs7039798
• ENST00000479147.6:n.216+135G>A

Variant summary

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

The ENST00000479147.6(FPGS):​n.216+135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,042 control chromosomes in the GnomAD database, including 18,406 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 0.48 (18402 hom., cov: 32)
  • Exomes 𝑓: 0.38 (4 hom.)
• Consequence: FPGS ENST00000479147.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 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+135G>A		intron_variant	Intron 1 of 7	5
FPGS	ENST00000479375.6	n.131+135G>A		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73262 AN: 151890 Hom.: 18377 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.382 AC: 13 AN: 34 Hom.: 4 AF XY: 0.393 AC XY: 11 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.318 AC: 7 AN: 22

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.482 AC: 73342 AN: 152008 Hom.: 18402 Cov.: 32 AF XY: 0.476 AC XY: 35397 AN XY: 74302

African (AFR) AF: 0.609 AC: 25237 AN: 41416

American (AMR) AF: 0.476 AC: 7270 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3468

East Asian (EAS) AF: 0.692 AC: 3573 AN: 5164

South Asian (SAS) AF: 0.385 AC: 1857 AN: 4826

European-Finnish (FIN) AF: 0.343 AC: 3625 AN: 10578

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28820 AN: 67976

Other (OTH) AF: 0.477 AC: 1006 AN: 2108

Alfa AF: 0.386 Hom.: 4512

Bravo AF: 0.503

Asia WGS AF: 0.520 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.54
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs7039798; hg19: chr9-130557226;