9-101442332-C-T

Variant names:

• chr9-101442332-C-T
• rs573816
• ENST00000648758.1:c.-79G>A

Variant summary

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

The ENST00000648758.1(ALDOB):​c.-79G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,026 control chromosomes in the GnomAD database, including 33,602 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 0.66 (33602 hom., cov: 32)
• Consequence: ALDOB ENST00000648758.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 3 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

LOC105376184 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648758.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOB	ENST00000648758.1		c.-79G>A		5_prime_UTR	Exon 1 of 9	ENSP00000497731.1	P05062
	ALDOB	ENST00000903779.1		c.-101G>A		5_prime_UTR	Exon 1 of 10	ENSP00000573838.1
	ALDOB	ENST00000648423.1		c.-133G>A		5_prime_UTR	Exon 1 of 4	ENSP00000497985.1	A0A3B3ITZ0

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100646 AN: 151908 Hom.: 33579 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.662 AC: 100712 AN: 152026 Hom.: 33602 Cov.: 32 AF XY: 0.659 AC XY: 48950 AN XY: 74306

African (AFR) AF: 0.612 AC: 25357 AN: 41442

American (AMR) AF: 0.624 AC: 9543 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2424 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2801 AN: 5154

South Asian (SAS) AF: 0.692 AC: 3332 AN: 4818

European-Finnish (FIN) AF: 0.655 AC: 6926 AN: 10576

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48031 AN: 67964

Other (OTH) AF: 0.685 AC: 1448 AN: 2114

Alfa AF: 0.689 Hom.: 104256

Bravo AF: 0.655

Asia WGS AF: 0.620 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.25
PhyloP100		-0.17
PromoterAI		0.00090	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs573816; hg19: chr9-104204614;