Genetic Variant ALDH1L1:n.1139G>A (chr3-126155545-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000476245.5(ALDH1L1):n.1139G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,554,482 control chromosomes in the GnomAD database, including 521,284 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 0.83 ( 52032 hom., cov: 33)

Exomes 𝑓: 0.82 ( 469252 hom. )

Consequence

ALDH1L1
ENST00000476245.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.56

Publications

19 publications found

Variant links:

Genes affected

ALDH1L1 (HGNC:3978): (aldehyde dehydrogenase 1 family member L1) The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ALDH1L1 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4 link	c.529-42G>A		intron_variant	Intron 4 of 22	ENST00000393434.7	NP_036322.2	O75891-1Q53H87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7 link	c.529-42G>A		intron_variant	Intron 4 of 22	1	NM_012190.4	ENSP00000377083.3		O75891-1

Frequencies

GnomAD3 genomes

AF:

0.827

AC:

125678

AN:

152046

Hom.:

51988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.859

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.894

Gnomad FIN

AF:

0.875

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.803

GnomAD2 exomes

AF:

0.832

AC:

177292

AN:

213166

AF XY:

0.834

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.844

Gnomad ASJ exome

AF:

0.844

Gnomad EAS exome

AF:

0.749

Gnomad FIN exome

AF:

0.875

Gnomad NFE exome

AF:

0.815

Gnomad OTH exome

AF:

0.827

GnomAD4 exome

AF:

0.817

AC:

1146022

AN:

1402318

Hom.:

469252

Cov.:

AF XY:

0.820

AC XY:

570686

AN XY:

696232

show subpopulations

African (AFR)

AF:

0.859

AC:

27457

AN:

31966

American (AMR)

AF:

0.837

AC:

33358

AN:

39846

Ashkenazi Jewish (ASJ)

AF:

0.839

AC:

19790

AN:

23580

East Asian (EAS)

AF:

0.711

AC:

27267

AN:

38336

South Asian (SAS)

AF:

0.899

AC:

70278

AN:

78160

European-Finnish (FIN)

AF:

0.870

AC:

43826

AN:

50372

Middle Eastern (MID)

AF:

0.833

AC:

4307

AN:

5170

European-Non Finnish (NFE)

AF:

0.810

AC:

872385

AN:

1076764

Other (OTH)

AF:

0.815

AC:

47354

AN:

58124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

10035

20070

30105

40140

50175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20308

40616

60924

81232

101540

<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:

0.827

AC:

125778

AN:

152164

Hom.:

52032

Cov.:

AF XY:

0.829

AC XY:

61683

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.849

AC:

35273

AN:

41526

American (AMR)

AF:

0.796

AC:

12185

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

2919

AN:

3472

East Asian (EAS)

AF:

0.745

AC:

3827

AN:

5140

South Asian (SAS)

AF:

0.895

AC:

4314

AN:

4820

European-Finnish (FIN)

AF:

0.875

AC:

9278

AN:

10604

Middle Eastern (MID)

AF:

0.782

AC:

230

AN:

294

European-Non Finnish (NFE)

AF:

0.813

AC:

55282

AN:

67984

Other (OTH)

AF:

0.801

AC:

1688

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1140

2280

3420

4560

5700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.818

Hom.:

94576

Bravo

AF:

0.822

Asia WGS

AF:

0.818

AC:

2845

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.47

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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