Genetic Variant ALDH1A1:c.504+90C>A (chr9-72927026-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000689.5(ALDH1A1):c.504+90C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 911,920 control chromosomes in the GnomAD database, including 109,853 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 15079 hom., cov: 32)

Exomes 𝑓: 0.50 ( 94774 hom. )

Consequence

ALDH1A1
NM_000689.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.536

Publications

14 publications found

Variant links:

Genes affected

ALDH1A1 (HGNC:402): (aldehyde dehydrogenase 1 family member A1) The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet. [provided by RefSeq, Mar 2011]

ALDH1A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000689.5. 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
	ALDH1A1	NM_000689.5	MANE Select	c.504+90C>A		intron	N/A	NP_000680.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.504+90C>A	intron	N/A	ENSP00000297785.3	P00352
ALDH1A1	ENST00000856212.1		c.594+90C>A	intron	N/A	ENSP00000526271.1
ALDH1A1	ENST00000966555.1		c.573+90C>A	intron	N/A	ENSP00000636614.1

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64934

AN:

151922

Hom.:

15071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.495

AC:

376180

AN:

759880

Hom.:

94774

Cov.:

AF XY:

0.495

AC XY:

194181

AN XY:

392250

show subpopulations

African (AFR)

AF:

0.218

AC:

4008

AN:

18400

American (AMR)

AF:

0.482

AC:

12651

AN:

26256

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

7546

AN:

16330

East Asian (EAS)

AF:

0.429

AC:

14903

AN:

34734

South Asian (SAS)

AF:

0.485

AC:

22904

AN:

47232

European-Finnish (FIN)

AF:

0.532

AC:

24755

AN:

46516

Middle Eastern (MID)

AF:

0.394

AC:

1463

AN:

3716

European-Non Finnish (NFE)

AF:

0.510

AC:

271208

AN:

531448

Other (OTH)

AF:

0.475

AC:

16742

AN:

35248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8900

17799

26699

35598

44498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5990

11980

17970

23960

29950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.427

AC:

64985

AN:

152040

Hom.:

15079

Cov.:

AF XY:

0.433

AC XY:

32185

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.236

AC:

9782

AN:

41464

American (AMR)

AF:

0.485

AC:

7411

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1550

AN:

3466

East Asian (EAS)

AF:

0.458

AC:

2367

AN:

5170

South Asian (SAS)

AF:

0.486

AC:

2339

AN:

4810

European-Finnish (FIN)

AF:

0.551

AC:

5821

AN:

10564

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34201

AN:

67980

Other (OTH)

AF:

0.434

AC:

917

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1805

3611

5416

7222

9027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.471

Hom.:

19254

Bravo

AF:

0.410

Asia WGS

AF:

0.419

AC:

1456

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.6

(source)

DANN

Benign

0.57

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over