Genetic Variant NM_000689.5:c.313-101T>A (chr9-72929122-A-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.313-101T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 1,320,226 control chromosomes in the GnomAD database, including 163,726 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 ( 15073 hom., cov: 32)

Exomes 𝑓: 0.50 ( 148653 hom. )

Consequence

ALDH1A1
NM_000689.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.330

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 (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.313-101T>A		intron_variant	Intron 3 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.313-101T>A		intron_variant	Intron 3 of 12	1	NM_000689.5	ENSP00000297785.3		P00352

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64921

AN:

151948

Hom.:

15065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.501

AC:

584866

AN:

1168160

Hom.:

148653

AF XY:

0.501

AC XY:

289117

AN XY:

577418

show subpopulations

African (AFR)

AF:

0.214

AC:

5584

AN:

26118

American (AMR)

AF:

0.483

AC:

13043

AN:

27030

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

9033

AN:

19676

East Asian (EAS)

AF:

0.434

AC:

14643

AN:

33734

South Asian (SAS)

AF:

0.491

AC:

30490

AN:

62158

European-Finnish (FIN)

AF:

0.530

AC:

18200

AN:

34322

Middle Eastern (MID)

AF:

0.395

AC:

1483

AN:

3752

European-Non Finnish (NFE)

AF:

0.514

AC:

468649

AN:

911708

Other (OTH)

AF:

0.478

AC:

23741

AN:

49662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

13257

26514

39770

53027

66284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13462

26924

40386

53848

67310

<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:

64972

AN:

152066

Hom.:

15073

Cov.:

AF XY:

0.433

AC XY:

32154

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.236

AC:

9779

AN:

41492

American (AMR)

AF:

0.486

AC:

7425

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1553

AN:

3472

East Asian (EAS)

AF:

0.456

AC:

2355

AN:

5160

South Asian (SAS)

AF:

0.486

AC:

2342

AN:

4820

European-Finnish (FIN)

AF:

0.550

AC:

5803

AN:

10546

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34199

AN:

67968

Other (OTH)

AF:

0.434

AC:

918

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1844

3688

5532

7376

9220

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:

0.448

Hom.:

2016

Bravo

AF:

0.410

Asia WGS

AF:

0.421

AC:

1462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.5

(source)

DANN

Benign

0.73

PhyloP100

0.33

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