rs1390694

Positions:

• chr1-59400083-A-G

Variant summary

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

The NM_018291.5(FGGY):​c.554+21246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,292 control chromosomes in the GnomAD database, including 108 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 0.033 (108 hom., cov: 32)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGGY	NM_018291.5	c.554+21246A>G		intron_variant		ENST00000303721.12	NP_060761.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGGY	ENST00000303721.12	c.554+21246A>G		intron_variant		1	NM_018291.5	ENSP00000305922	P1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4973 AN: 152174 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0393

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

GnomAD4 genome AF: 0.0327 AC: 4978 AN: 152292 Hom.: 108 Cov.: 32 AF XY: 0.0334 AC XY: 2487 AN XY: 74468

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.000577

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0346 Hom.: 7

Bravo AF: 0.0293

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.5
DANN	Benign	0.59

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: rs1390694; hg19: chr1-59865755;