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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new If you want to explore the variant's impact on the transcript ENST00000479147.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479147.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FPGS	NM_004957.6	MANE Select	c.-157C>T	upstream_gene	N/A	NP_004948.4
FPGS	NM_001288803.1		c.-157C>T	upstream_gene	N/A	NP_001275732.1	Q05932-4
FPGS	NR_110170.1		n.-90C>T	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FPGS	ENST00000479147.6	TSL:5	n.217-1517C>T	intron	N/A
FPGS	ENST00000479375.6	TSL:5	n.132-1517C>T	intron	N/A
FPGS	ENST00000373247.7	TSL:1 MANE Select	c.-157C>T	upstream_gene	N/A	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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over