9-101433826-C-T

Position:

• chr9-101433826-C-T

Variant summary

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

The NM_000035.4(ALDOB):​c.-11+1883G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,800 control chromosomes in the GnomAD database, including 30,673 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 0.63 (30673 hom., cov: 30)
• Consequence: ALDOB NM_000035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

Genes affected

ALDOB (HGNC:417): (aldolase, fructose-bisphosphate B) Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a tetrameric glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Vertebrates have 3 aldolase isozymes which are distinguished by their electrophoretic and catalytic properties. Differences indicate that aldolases A, B, and C are distinct proteins, the products of a family of related 'housekeeping' genes exhibiting developmentally regulated expression of the different isozymes. The developing embryo produces aldolase A, which is produced in even greater amounts in adult muscle where it can be as much as 5% of total cellular protein. In adult liver, kidney and intestine, aldolase A expression is repressed and aldolase B is produced. In brain and other nervous tissue, aldolase A and C are expressed about equally. There is a high degree of homology between aldolase A and C. Defects in ALDOB cause hereditary fructose intolerance. [provided by RefSeq, Dec 2008]

ALDOB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDOB	NM_000035.4	c.-11+1883G>A		intron_variant		ENST00000647789.2	NP_000026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDOB	ENST00000647789.2	c.-11+1883G>A		intron_variant			NM_000035.4	ENSP00000497767.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95697 AN: 151682 Hom.: 30658 Cov.: 30

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.631 AC: 95756 AN: 151800 Hom.: 30673 Cov.: 30 AF XY: 0.626 AC XY: 46410 AN XY: 74180

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.662

Alfa AF: 0.648 Hom.: 3822

Bravo AF: 0.633

Asia WGS AF: 0.498 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.071
DANN	Benign	0.23

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: rs970385; hg19: chr9-104196108;