rs835367

chr1-59296796-A-Gchr1-59296796-A-T

Variant summary

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

The ENST00000413489.5(FGGY):c.-126A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 150,220 control chromosomes in the GnomAD database, including 14,526 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 (14485 hom., cov: 32)
  • Exomes 𝑓: 0.27 (41 hom.)
• Consequence: FGGY ENST00000413489.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGGY	XM_011541731.2	c.-15+336A>G		intron_variant
FGGY	NM_001350793.2			upstream_gene_variant
FGGY	NM_001350796.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGGY	ENST00000413489.5	c.-126A>G		5_prime_UTR_variant	1/5	3
FGGY	ENST00000582567.1	c.-242A>G		5_prime_UTR_variant	1/3	4
FGGY	ENST00000474476.5			upstream_gene_variant		5
FGGY	ENST00000634606.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63211 AN: 149638 Hom.: 14464 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.272 AC: 132 AN: 486 Hom.: 41 Cov.: 0 AF XY: 0.290 AC XY: 106 AN XY: 366

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.423 AC: 63290 AN: 149734 Hom.: 14485 Cov.: 32 AF XY: 0.428 AC XY: 31275 AN XY: 73122

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.382

Alfa AF: 0.369 Hom.: 3855

Bravo AF: 0.426

Asia WGS AF: 0.351 AC: 991 AN: 2814

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	6.0
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs835367; hg19: chr1-59762468;