dbSNP rs13959: ALDH1A1:p.Ser75Ser (chr9-72930966-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000689.5(ALDH1A1):c.225C>T(p.Ser75Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,613,406 control chromosomes in the GnomAD database, including 199,816 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 ( 15080 hom., cov: 32)

Exomes 𝑓: 0.50 ( 184736 hom. )

Consequence

ALDH1A1
NM_000689.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

43 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-1.53 with no splicing effect.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5 link	c.225C>T	p.Ser75Ser	synonymous_variant	Exon 3 of 13	ENST00000297785.8	NP_000680.2	P00352V9HW83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8 link	c.225C>T	p.Ser75Ser	synonymous_variant	Exon 3 of 13	1	NM_000689.5	ENSP00000297785.3		P00352

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64933

AN:

151826

Hom.:

15072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.360

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.436

GnomAD2 exomes

AF:

0.476

AC:

119437

AN:

250974

AF XY:

0.481

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.498

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.500

AC:

730120

AN:

1461462

Hom.:

184736

Cov.:

AF XY:

0.500

AC XY:

363283

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.215

AC:

7181

AN:

33454

American (AMR)

AF:

0.484

AC:

21645

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

11982

AN:

26128

East Asian (EAS)

AF:

0.434

AC:

17224

AN:

39688

South Asian (SAS)

AF:

0.490

AC:

42212

AN:

86224

European-Finnish (FIN)

AF:

0.531

AC:

28348

AN:

53398

Middle Eastern (MID)

AF:

0.393

AC:

2269

AN:

5768

European-Non Finnish (NFE)

AF:

0.513

AC:

570457

AN:

1111736

Other (OTH)

AF:

0.477

AC:

28802

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

19039

38079

57118

76158

95197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.428

AC:

64984

AN:

151944

Hom.:

15080

Cov.:

AF XY:

0.433

AC XY:

32158

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.236

AC:

9795

AN:

41456

American (AMR)

AF:

0.486

AC:

7412

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1553

AN:

3470

East Asian (EAS)

AF:

0.459

AC:

2359

AN:

5144

South Asian (SAS)

AF:

0.487

AC:

2344

AN:

4818

European-Finnish (FIN)

AF:

0.552

AC:

5812

AN:

10538

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.503

AC:

34194

AN:

67934

Other (OTH)

AF:

0.434

AC:

917

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1813

3625

5438

7250

9063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.467

Hom.:

55819

Bravo

AF:

0.411

Asia WGS

AF:

0.426

AC:

1479

AN:

3478

EpiCase

AF:

0.489

EpiControl

AF:

0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

(source)

DANN

Benign

0.88

PhyloP100

-1.5

Mutation Taster

=98/2

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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rs13959

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