Genetic Variant ALDH1A1:c.1201-109C>A (chr9-72909868-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.1201-109C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 952,984 control chromosomes in the GnomAD database, including 125,865 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 0.55 ( 23791 hom., cov: 32)

Exomes 𝑓: 0.50 ( 102074 hom. )

Consequence

ALDH1A1
NM_000689.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

18 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	NM_000689.5	MANE Select	c.1201-109C>A		intron	N/A	NP_000680.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.1201-109C>A		intron	N/A	ENSP00000297785.3

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83854

AN:

151798

Hom.:

23760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.500

AC:

400921

AN:

801068

Hom.:

102074

AF XY:

0.497

AC XY:

200956

AN XY:

404026

show subpopulations

African (AFR)

AF:

0.707

AC:

12265

AN:

17350

American (AMR)

AF:

0.498

AC:

8921

AN:

17910

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

6391

AN:

15360

East Asian (EAS)

AF:

0.548

AC:

16519

AN:

30120

South Asian (SAS)

AF:

0.407

AC:

18147

AN:

44636

European-Finnish (FIN)

AF:

0.522

AC:

15516

AN:

29750

Middle Eastern (MID)

AF:

0.513

AC:

1293

AN:

2520

European-Non Finnish (NFE)

AF:

0.500

AC:

303463

AN:

606972

Other (OTH)

AF:

0.505

AC:

18406

AN:

36450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9311

18621

27932

37242

46553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7640

15280

22920

30560

38200

<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:

0.552

AC:

83932

AN:

151916

Hom.:

23791

Cov.:

AF XY:

0.550

AC XY:

40790

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.693

AC:

28734

AN:

41472

American (AMR)

AF:

0.504

AC:

7688

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1474

AN:

3468

East Asian (EAS)

AF:

0.522

AC:

2692

AN:

5160

South Asian (SAS)

AF:

0.415

AC:

1998

AN:

4812

European-Finnish (FIN)

AF:

0.506

AC:

5321

AN:

10524

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34318

AN:

67904

Other (OTH)

AF:

0.539

AC:

1138

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1892

3785

5677

7570

9462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.525

Hom.:

39548

Bravo

AF:

0.561

Asia WGS

AF:

0.534

AC:

1856

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

(source)

DANN

Benign

0.74

PhyloP100

-1.2

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