rs4451422

chr9-127814318-A-Cchr9-127814318-A-G

Variant summary

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

The XM_005251864.5(FPGS):c.*91A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 226,298 control chromosomes in the GnomAD database, including 20,447 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 (13829 hom., cov: 32)
  • Exomes 𝑓: 0.41 (6618 hom.)
• Consequence: FPGS XM_005251864.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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=-0.91).
• 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	UniProt
FPGS	XM_005251864.5	c.*91A>C		3_prime_UTR_variant	16/16
FPGS	XM_047423127.1	c.*91A>C		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPGS	ENST00000467826.5	n.820A>C		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64218 AN: 151906 Hom.: 13815 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.412 AC: 30601 AN: 74274 Hom.: 6618 Cov.: 4 AF XY: 0.411 AC XY: 14668 AN XY: 35674

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.413

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.423 AC: 64276 AN: 152024 Hom.: 13829 Cov.: 32 AF XY: 0.419 AC XY: 31112 AN XY: 74324

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.431

Alfa AF: 0.407 Hom.: 17852

Bravo AF: 0.439

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.7
Dann	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4451422; hg19: chr9-130576597;