rs10118903

Variant names:

• chr9-127802768-C-T
• rs10118903
• ENST00000479147.6:n.217-1517C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 2 publications found

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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
	FPGS	NR_110170.1		n.-90C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 6820 AN: 121954 Hom.: 516 Cov.: 25

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

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: 21 AN: 10392

East Asian (EAS) AF: 0.000230 AC: 5 AN: 21696

South Asian (SAS) AF: 0.0234 AC: 314 AN: 13396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21694

Middle Eastern (MID) AF: 0.0150 AC: 27 AN: 1802

European-Non Finnish (NFE) AF: 0.000440 AC: 183 AN: 415450

Other (OTH) AF: 0.0121 AC: 302 AN: 24922

GnomAD4 genome AF: 0.0560 AC: 6832 AN: 122042 Hom.: 521 Cov.: 25 AF XY: 0.0572 AC XY: 3267 AN XY: 57088

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: 6 AN: 3058

East Asian (EAS) AF: 0.00291 AC: 10 AN: 3436

South Asian (SAS) AF: 0.0370 AC: 122 AN: 3294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5818

Middle Eastern (MID) AF: 0.0259 AC: 6 AN: 232

European-Non Finnish (NFE) AF: 0.000946 AC: 56 AN: 59200

Other (OTH) AF: 0.0453 AC: 77 AN: 1698

Alfa AF: 0.0375 Hom.: 61

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
DANN	Benign	0.65
PhyloP100		-2.1
PromoterAI		0.0015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10118903; hg19: chr9-130565047;