Variant chr9-101430914-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting

The NM_000035.4(ALDOB):c.-10-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,556,002 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 4 hom. )

Consequence

ALDOB
NM_000035.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.526

Variant links:

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 links:

ALDOB (HGNC:):

ALDOB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-101430914-G-A is Benign according to our data. Variant chr9-101430914-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 254729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDOB	NM_000035.4 linkuse as main transcript	c.-10-17C>T		intron_variant		ENST00000647789.2	NP_000026.2	P05062A0A024R145

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDOB	ENST00000647789.2 linkuse as main transcript	c.-10-17C>T		intron_variant			NM_000035.4	ENSP00000497767.1		P05062

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00184

AC:

460

AN:

249968

Hom.:

AF XY:

0.00185

AC XY:

250

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000813

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.000789

Gnomad FIN exome

AF:

0.00335

Gnomad NFE exome

AF:

0.00282

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00198

AC:

2784

AN:

1403776

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1332

AN XY:

701824

show subpopulations

Gnomad4 AFR exome

AF:

0.000372

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.000647

Gnomad4 FIN exome

AF:

0.00328

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00173

AC:

263

AN:

152226

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00256

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00145

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over