rs515313

Variant names:

• chr9-101435495-C-T
• rs515313
• NM_000035.4:c.-11+214G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Ambry Genetics, Myriad Women’s Health, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000035.4. 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
	ALDOB	NM_000035.4	MANE Select	c.-11+214G>A		intron	N/A	NP_000026.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOB	ENST00000647789.2	MANE Select	c.-11+214G>A		intron	N/A	ENSP00000497767.1
	ALDOB	ENST00000648064.1		c.-10-4598G>A		intron	N/A	ENSP00000497990.1
	ALDOB	ENST00000648758.1		c.-10-4598G>A		intron	N/A	ENSP00000497731.1

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

African (AFR) AF: 0.394 AC: 16280 AN: 41370

American (AMR) AF: 0.348 AC: 5314 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2393 AN: 5144

South Asian (SAS) AF: 0.520 AC: 2502 AN: 4816

European-Finnish (FIN) AF: 0.374 AC: 3925 AN: 10488

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.314 AC: 21361 AN: 67944

Other (OTH) AF: 0.331 AC: 697 AN: 2106

Alfa AF: 0.340 Hom.: 1153

Bravo AF: 0.352

Asia WGS AF: 0.495 AC: 1720 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.55
PhyloP100		-0.19
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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