chr1-59387647-A-G

Position:

• chr1-59387647-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+8810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,136 control chromosomes in the GnomAD database, including 2,811 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 0.17 (2811 hom., cov: 32)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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]

FGGY (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGGY	NM_018291.5	c.554+8810A>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+8810A>G		intron_variant		1	NM_018291.5	ENSP00000305922.8

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25940 AN: 152018 Hom.: 2815 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.170 AC: 25934 AN: 152136 Hom.: 2811 Cov.: 32 AF XY: 0.178 AC XY: 13253 AN XY: 74352

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.173

Alfa AF: 0.188 Hom.: 2493

Bravo AF: 0.160

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
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: rs7534016; hg19: chr1-59853319;