1-59387647-A-G

Variant names:

• chr1-59387647-A-G
• rs7534016
• NM_018291.5:c.554+8810A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018291.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGGY	NM_018291.5	MANE Select	c.554+8810A>G		intron	N/A	NP_060761.3
	FGGY	NM_001113411.2		c.554+8810A>G		intron	N/A	NP_001106882.1
	FGGY	NM_001350790.2		c.554+8810A>G		intron	N/A	NP_001337719.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGGY	ENST00000303721.12	TSL:1 MANE Select	c.554+8810A>G		intron	N/A	ENSP00000305922.8
	FGGY	ENST00000371218.8	TSL:1	c.554+8810A>G		intron	N/A	ENSP00000360262.4
	FGGY	ENST00000371212.5	TSL:2	c.290+8810A>G		intron	N/A	ENSP00000360256.1

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

African (AFR) AF: 0.0390 AC: 1621 AN: 41546

American (AMR) AF: 0.223 AC: 3403 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1844 AN: 5164

South Asian (SAS) AF: 0.308 AC: 1488 AN: 4826

European-Finnish (FIN) AF: 0.259 AC: 2738 AN: 10572

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13615 AN: 67970

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.174 Hom.: 3984

Bravo AF: 0.160

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.45
PhyloP100		-0.34
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: rs7534016; hg19: chr1-59853319;