rs515313

Positions:

• chr9-101435495-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000035.4(ALDOB):​c.-11+214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,798 control chromosomes in the GnomAD database, including 9,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (9966 hom., cov: 31)
• Consequence: ALDOB NM_000035.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.190

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-101435495-C-T is Benign according to our data. Variant chr9-101435495-C-T is described in ClinVar as [Benign]. Clinvar id is 1275044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDOB	NM_000035.4	c.-11+214G>A		intron_variant		ENST00000647789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDOB	ENST00000647789.2	c.-11+214G>A		intron_variant			NM_000035.4	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54050 AN: 151680 Hom.: 9958 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.356 AC: 54075 AN: 151798 Hom.: 9966 Cov.: 31 AF XY: 0.362 AC XY: 26841 AN XY: 74174

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.331

Alfa AF: 0.338 Hom.: 1098

Bravo AF: 0.352

Asia WGS AF: 0.495 AC: 1720 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.55

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: rs515313; hg19: chr9-104197777; COSMIC: COSV66397585;