rs17119280

Variant names:

• chr1-59333489-G-A
• rs17119280
• NM_018291.5:c.202-6469G>A

Variant summary

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

The NM_018291.5(FGGY):​c.202-6469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 152,282 control chromosomes in the GnomAD database, including 95 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 0.021 (95 hom., cov: 33)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 10 publications found

Genes affected

FGGY (HGNC:25610): (FGGY carbohydrate kinase domain containing) This gene encodes a protein that phosphorylates carbohydrates such as ribulose, ribitol, and L-arabinitol. Genome-wide association studies in some populations have found an association between polymorphisms in this gene and sporadic amyotrophic lateral sclerosis, but studies of other populations have not been able to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGGY	NM_018291.5	c.202-6469G>A		intron_variant	Intron 2 of 15	ENST00000303721.12	NP_060761.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGGY	ENST00000303721.12	c.202-6469G>A		intron_variant	Intron 2 of 15	1	NM_018291.5	ENSP00000305922.8

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3213 AN: 152164 Hom.: 95 Cov.: 33

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0212 AC: 3225 AN: 152282 Hom.: 95 Cov.: 33 AF XY: 0.0200 AC XY: 1489 AN XY: 74450

African (AFR) AF: 0.0710 AC: 2950 AN: 41542

American (AMR) AF: 0.00896 AC: 137 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5180

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68036

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00935 Hom.: 87

Bravo AF: 0.0233

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.42
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17119280; hg19: chr1-59799161;