dbSNP rs2290053: ALDH1L1:c.2082+140G>A (chr3-126114417-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 NM_012190.4(ALDH1L1):c.2082+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 581,716 control chromosomes in the GnomAD database, including 64,042 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 0.47 ( 16891 hom., cov: 33)

Exomes 𝑓: 0.46 ( 47151 hom. )

Consequence

ALDH1L1
NM_012190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.656

Publications

9 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4 link	c.2082+140G>A		intron_variant	Intron 18 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.2082+140G>A		intron_variant	Intron 18 of 22	1	NM_012190.4	ENSP00000377083.3		O75891-1

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71463

AN:

151908

Hom.:

16874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.462

AC:

198718

AN:

429688

Hom.:

47151

AF XY:

0.463

AC XY:

99398

AN XY:

214852

show subpopulations

African (AFR)

AF:

0.468

AC:

5272

AN:

11274

American (AMR)

AF:

0.380

AC:

4138

AN:

10894

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

5351

AN:

10620

East Asian (EAS)

AF:

0.317

AC:

8085

AN:

25524

South Asian (SAS)

AF:

0.377

AC:

4355

AN:

11540

European-Finnish (FIN)

AF:

0.490

AC:

13755

AN:

28078

Middle Eastern (MID)

AF:

0.512

AC:

911

AN:

1780

European-Non Finnish (NFE)

AF:

0.476

AC:

146312

AN:

307298

Other (OTH)

AF:

0.465

AC:

10539

AN:

22680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4961

9922

14882

19843

24804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2856

5712

8568

11424

14280

<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:

0.470

AC:

71518

AN:

152028

Hom.:

16891

Cov.:

AF XY:

0.465

AC XY:

34563

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.473

AC:

19606

AN:

41466

American (AMR)

AF:

0.410

AC:

6275

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1782

AN:

3468

East Asian (EAS)

AF:

0.367

AC:

1897

AN:

5166

South Asian (SAS)

AF:

0.395

AC:

1900

AN:

4808

European-Finnish (FIN)

AF:

0.490

AC:

5179

AN:

10560

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33312

AN:

67956

Other (OTH)

AF:

0.470

AC:

993

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1962

3923

5885

7846

9808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.482

Hom.:

75129

Bravo

AF:

0.465

Asia WGS

AF:

0.419

AC:

1454

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.80

(source)

DANN

Benign

0.78

PhyloP100

-0.66

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