rs4451422

Variant summary

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

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.443
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]

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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=-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 rank MANE Protein UniProt
FPGSNM_004957.6 linkc.*714A>C downstream_gene_variant ENST00000373247.7 NP_004948.4 Q05932-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FPGSENST00000467826.5 linkn.820A>C non_coding_transcript_exon_variant Exon 8 of 8 5
FPGSENST00000373247.7 linkc.*714A>C downstream_gene_variant 1 NM_004957.6 ENSP00000362344.2 Q05932-1
FPGSENST00000393706.6 linkc.*714A>C downstream_gene_variant 2 ENSP00000377309.2 Q05932-4
FPGSENST00000630236.2 linkc.*1202A>C downstream_gene_variant 5 ENSP00000486766.1 Q5JU23

Frequencies

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

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

Other links and lift over

dbSNP: rs4451422; hg19: chr9-130576597; API