dbSNP rs348472: ALDH1A1:c.1359-112T>C (chr9-72906144-A-G) – 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.1359-112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 687,852 control chromosomes in the GnomAD database, including 294,386 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 0.86 ( 57835 hom., cov: 30)

Exomes 𝑓: 0.94 ( 236551 hom. )

Consequence

ALDH1A1
NM_000689.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.385

Publications

9 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 (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5 link	c.1359-112T>C		intron_variant	Intron 11 of 12	ENST00000297785.8	NP_000680.2	P00352V9HW83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8 link	c.1359-112T>C		intron_variant	Intron 11 of 12	1	NM_000689.5	ENSP00000297785.3		P00352

Frequencies

GnomAD3 genomes

AF:

0.861

AC:

130908

AN:

151974

Hom.:

57818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.932

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.992

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.975

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.950

Gnomad OTH

AF:

0.886

GnomAD4 exome

AF:

0.938

AC:

502333

AN:

535760

Hom.:

236551

AF XY:

0.935

AC XY:

265679

AN XY:

284044

show subpopulations

African (AFR)

AF:

0.652

AC:

8685

AN:

13312

American (AMR)

AF:

0.945

AC:

17606

AN:

18640

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

12823

AN:

15354

East Asian (EAS)

AF:

0.993

AC:

30312

AN:

30536

South Asian (SAS)

AF:

0.883

AC:

37492

AN:

42470

European-Finnish (FIN)

AF:

0.976

AC:

43672

AN:

44754

Middle Eastern (MID)

AF:

0.894

AC:

3347

AN:

3744

European-Non Finnish (NFE)

AF:

0.952

AC:

322413

AN:

338532

Other (OTH)

AF:

0.914

AC:

25983

AN:

28418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1376

2752

4129

5505

6881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2668

5336

8004

10672

13340

<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:

0.861

AC:

130976

AN:

152092

Hom.:

57835

Cov.:

AF XY:

0.865

AC XY:

64274

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.640

AC:

26522

AN:

41448

American (AMR)

AF:

0.932

AC:

14233

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

2866

AN:

3472

East Asian (EAS)

AF:

0.992

AC:

5127

AN:

5170

South Asian (SAS)

AF:

0.893

AC:

4306

AN:

4824

European-Finnish (FIN)

AF:

0.975

AC:

10344

AN:

10604

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.950

AC:

64588

AN:

67992

Other (OTH)

AF:

0.887

AC:

1869

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

768

1537

2305

3074

3842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.924

Hom.:

115098

Bravo

AF:

0.849

Asia WGS

AF:

0.924

AC:

3212

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.1

(source)

DANN

Benign

0.60

PhyloP100

-0.39

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over