1-59460280-G-C

Position:

• chr1-59460280-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018291.5(FGGY):​c.670+3204G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,958 control chromosomes in the GnomAD database, including 15,732 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 0.45 (15732 hom., cov: 31)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGGY	NM_018291.5	c.670+3204G>C		intron_variant		ENST00000303721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGGY	ENST00000303721.12	c.670+3204G>C		intron_variant		1	NM_018291.5	P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68631 AN: 151840 Hom.: 15710 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.452 AC: 68697 AN: 151958 Hom.: 15732 Cov.: 31 AF XY: 0.447 AC XY: 33181 AN XY: 74284

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.471

Alfa AF: 0.285 Hom.: 622

Bravo AF: 0.463

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs7533447; hg19: chr1-59925952;