rs12337537

Positions:

• chr9-101435909-A-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000648064.1(ALDOB):​c.-10-5012T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 152,174 control chromosomes in the GnomAD database, including 929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (929 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: ALDOB ENST00000648064.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.75

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 9-101435909-A-T is Benign according to our data. Variant chr9-101435909-A-T is described in ClinVar as [Benign]. Clinvar id is 254730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.101435909A>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDOB	ENST00000648064.1	c.-10-5012T>A		intron_variant				ENSP00000497990.1
ALDOB	ENST00000648758.1	c.-10-5012T>A		intron_variant				ENSP00000497731.1
ALDOB	ENST00000648423.1	c.-64-147T>A		intron_variant				ENSP00000497985.1

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14802 AN: 152044 Hom.: 928 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.0973 AC: 14799 AN: 152162 Hom.: 929 Cov.: 32 AF XY: 0.0986 AC XY: 7335 AN XY: 74390

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.107

Alfa AF: 0.117 Hom.: 152

Bravo AF: 0.0897

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Jan 27, 2016	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12337537; hg19: chr9-104198191;