rs1929480

Positions:

• chr9-101427398-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000035.4(ALDOB):​c.540+84A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,519,468 control chromosomes in the GnomAD database, including 82,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6012 hom., cov: 32)
  • Exomes 𝑓: 0.32 (76225 hom.)
• Consequence: ALDOB NM_000035.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.622

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-101427398-T-G is Benign according to our data. Variant chr9-101427398-T-G is described in ClinVar as [Benign]. Clinvar id is 1177040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDOB	NM_000035.4	c.540+84A>C		intron_variant		ENST00000647789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDOB	ENST00000647789.2	c.540+84A>C		intron_variant			NM_000035.4	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38204 AN: 151980 Hom.: 6013 Cov.: 32

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.323 AC: 441825 AN: 1367370 Hom.: 76225 AF XY: 0.322 AC XY: 219739 AN XY: 682806

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.0663

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.251 AC: 38200 AN: 152098 Hom.: 6012 Cov.: 32 AF XY: 0.246 AC XY: 18289 AN XY: 74348

Gnomad4 AFR AF: 0.0811

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.290

Alfa AF: 0.304 Hom.: 1302

Bravo AF: 0.241

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary fructosuria Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.46

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: rs1929480; hg19: chr9-104189680;