rs12727131

Variant names:

• chr1-59618844-G-A
• rs12727131
• NM_018291.5:c.1012-7144G>A

Variant summary

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

The NM_018291.5(FGGY):​c.1012-7144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 151,978 control chromosomes in the GnomAD database, including 856 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 0.099 (856 hom., cov: 32)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881
• Publications: 9 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 (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGGY	NM_018291.5	c.1012-7144G>A		intron_variant	Intron 9 of 15	ENST00000303721.12	NP_060761.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGGY	ENST00000303721.12	c.1012-7144G>A		intron_variant	Intron 9 of 15	1	NM_018291.5	ENSP00000305922.8

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15062 AN: 151860 Hom.: 852 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0952

Gnomad ASJ AF: 0.0840

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.0768

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

GnomAD4 genome AF: 0.0992 AC: 15080 AN: 151978 Hom.: 856 Cov.: 32 AF XY: 0.102 AC XY: 7565 AN XY: 74282

African (AFR) AF: 0.0889 AC: 3687 AN: 41470

American (AMR) AF: 0.0949 AC: 1446 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0840 AC: 291 AN: 3464

East Asian (EAS) AF: 0.153 AC: 791 AN: 5166

South Asian (SAS) AF: 0.286 AC: 1383 AN: 4830

European-Finnish (FIN) AF: 0.0835 AC: 884 AN: 10582

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

European-Non Finnish (NFE) AF: 0.0933 AC: 6334 AN: 67918

Other (OTH) AF: 0.0812 AC: 171 AN: 2106

Alfa AF: 0.0965 Hom.: 1487

Bravo AF: 0.0939

Asia WGS AF: 0.189 AC: 655 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	3.1
DANN	Benign	0.63
PhyloP100		0.88
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: rs12727131; hg19: chr1-60084516;