dbSNP rs10118903: FPGS:n.217-1517C>T (chr9-127802768-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000479147.6(FPGS):n.217-1517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 649,534 control chromosomes in the GnomAD database, including 673 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 0.056 ( 521 hom., cov: 25)

Exomes 𝑓: 0.0051 ( 152 hom. )

Consequence

FPGS
ENST00000479147.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

2 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
FPGS	NM_004957.6 link	c.-157C>T	upstream_gene_variant	ENST00000373247.7	NP_004948.4	Q05932-1
FPGS	NM_001288803.1 link	c.-157C>T	upstream_gene_variant		NP_001275732.1	Q05932-4
FPGS	NR_110170.1 link	n.-90C>T	upstream_gene_variant
FPGS	XM_005251864.5 link	c.-157C>T	upstream_gene_variant		XP_005251921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000373247.7 link	c.-157C>T		upstream_gene_variant		1	NM_004957.6	ENSP00000362344.2		Q05932-1

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

6820

AN:

121954

Hom.:

516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.00196

Gnomad EAS

AF:

0.00291

Gnomad SAS

AF:

0.0377

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0236

Gnomad NFE

AF:

0.000946

Gnomad OTH

AF:

0.0458

GnomAD4 exome

AF:

0.00509

AC:

2686

AN:

527492

Hom.:

152

AF XY:

0.00480

AC XY:

1245

AN XY:

259458

show subpopulations

African (AFR)

AF:

0.154

AC:

1719

AN:

11168

American (AMR)

AF:

0.0165

AC:

115

AN:

6972

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

10392

East Asian (EAS)

AF:

0.000230

AC:

AN:

21696

South Asian (SAS)

AF:

0.0234

AC:

314

AN:

13396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21694

Middle Eastern (MID)

AF:

0.0150

AC:

AN:

1802

European-Non Finnish (NFE)

AF:

0.000440

AC:

183

AN:

415450

Other (OTH)

AF:

0.0121

AC:

302

AN:

24922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

119

238

356

475

594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0560

AC:

6832

AN:

122042

Hom.:

521

Cov.:

AF XY:

0.0572

AC XY:

3267

AN XY:

57088

show subpopulations

African (AFR)

AF:

0.185

AC:

6286

AN:

34000

American (AMR)

AF:

0.0256

AC:

269

AN:

10526

Ashkenazi Jewish (ASJ)

AF:

0.00196

AC:

AN:

3058

East Asian (EAS)

AF:

0.00291

AC:

AN:

3436

South Asian (SAS)

AF:

0.0370

AC:

122

AN:

3294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5818

Middle Eastern (MID)

AF:

0.0259

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.000946

AC:

AN:

59200

Other (OTH)

AF:

0.0453

AC:

AN:

1698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

281

562

844

1125

1406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0375

Hom.:

Bravo

AF:

0.0543

Asia WGS

AF:

0.0300

AC:

104

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.7

(source)

DANN

Benign

0.65

PhyloP100

-2.1

PromoterAI

0.0015

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over