9-101433826-C-T

Variant names:

• chr9-101433826-C-T
• rs970385
• NM_000035.4:c.-11+1883G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• hereditary fructose intolerance

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000035.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOB	NM_000035.4	MANE Select	c.-11+1883G>A		intron	N/A	NP_000026.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOB	ENST00000647789.2	MANE Select	c.-11+1883G>A		intron	N/A	ENSP00000497767.1	P05062
	ALDOB	ENST00000903788.1		c.-2939G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000573847.1
	ALDOB	ENST00000903789.1		c.-121G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000573848.1

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

African (AFR) AF: 0.563 AC: 23269 AN: 41358

American (AMR) AF: 0.647 AC: 9877 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2409 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2737 AN: 5118

South Asian (SAS) AF: 0.479 AC: 2298 AN: 4798

European-Finnish (FIN) AF: 0.626 AC: 6603 AN: 10542

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46513 AN: 67940

Other (OTH) AF: 0.662 AC: 1397 AN: 2110

Alfa AF: 0.646 Hom.: 3951

Bravo AF: 0.633

Asia WGS AF: 0.498 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.071
DANN	Benign	0.23
PhyloP100		-3.7
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: rs970385; hg19: chr9-104196108;