9-127794947-G-A

Position:

• chr9-127794947-G-A

Variant summary

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

The ENST00000479147.6(FPGS):​n.216+135G>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000479147.6	n.216+135G>A		intron_variant, non_coding_transcript_variant		5
FPGS	ENST00000479375.6	n.131+135G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.833

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

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.477

Alfa AF: 0.380 Hom.: 3802

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7039798; hg19: chr9-130557226;