dbSNP rs7039798: FPGS:n.216+135G>A (chr9-127794947-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Variant links:

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]

FPGS links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000479147.6 link	n.216+135G>A		intron_variant	Intron 1 of 7	5
FPGS	ENST00000479375.6 link	n.131+135G>A		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73262

AN:

151890

Hom.:

18377

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.393

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.476

AC XY:

35397

AN XY:

74302

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over