chr1-59750274-C-T

Variant names:

• chr1-59750274-C-T
• rs10489423
• NM_018291.5:c.1513-7657C>T

Variant summary

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

The NM_018291.5(FGGY):​c.1513-7657C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,128 control chromosomes in the GnomAD database, including 248 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 0.045 (248 hom., cov: 32)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGGY	NM_018291.5	c.1513-7657C>T		intron_variant	Intron 14 of 15	ENST00000303721.12	NP_060761.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGGY	ENST00000303721.12	c.1513-7657C>T		intron_variant	Intron 14 of 15	1	NM_018291.5	ENSP00000305922.8

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6850 AN: 152010 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0450 AC: 6848 AN: 152128 Hom.: 248 Cov.: 32 AF XY: 0.0470 AC XY: 3496 AN XY: 74380

African (AFR) AF: 0.0750 AC: 3110 AN: 41486

American (AMR) AF: 0.0928 AC: 1418 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.134 AC: 694 AN: 5170

South Asian (SAS) AF: 0.0656 AC: 316 AN: 4814

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10586

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 915 AN: 68012

Other (OTH) AF: 0.0516 AC: 109 AN: 2112

Alfa AF: 0.0280 Hom.: 174

Bravo AF: 0.0536

Asia WGS AF: 0.104 AC: 362 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	0.21
DANN	Benign	0.69
PhyloP100		-1.4
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: rs10489423; hg19: chr1-60215946;