Genetic Variant ALDH1L1:c.1623+126G>A (chr3-126131258-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.1623+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,226,954 control chromosomes in the GnomAD database, including 236,281 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 0.63 ( 30669 hom., cov: 34)

Exomes 𝑓: 0.61 ( 205612 hom. )

Consequence

ALDH1L1
NM_012190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.483

Publications

3 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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4 link	c.1623+126G>A		intron_variant	Intron 13 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.1623+126G>A		intron_variant	Intron 13 of 22	1	NM_012190.4	ENSP00000377083.3		O75891-1

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96343

AN:

151818

Hom.:

30654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.651

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.611

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.657

GnomAD4 exome

AF:

0.614

AC:

660232

AN:

1075018

Hom.:

205612

AF XY:

0.611

AC XY:

322959

AN XY:

528262

show subpopulations

African (AFR)

AF:

0.639

AC:

15366

AN:

24032

American (AMR)

AF:

0.429

AC:

10840

AN:

25256

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

10692

AN:

16142

East Asian (EAS)

AF:

0.557

AC:

18769

AN:

33696

South Asian (SAS)

AF:

0.413

AC:

19849

AN:

48036

European-Finnish (FIN)

AF:

0.603

AC:

25512

AN:

42320

Middle Eastern (MID)

AF:

0.650

AC:

2546

AN:

3916

European-Non Finnish (NFE)

AF:

0.632

AC:

529363

AN:

837158

Other (OTH)

AF:

0.614

AC:

27295

AN:

44462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

10936

21872

32807

43743

54679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14622

29244

43866

58488

73110

<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:

0.634

AC:

96401

AN:

151936

Hom.:

30669

Cov.:

AF XY:

0.629

AC XY:

46682

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.651

AC:

26957

AN:

41426

American (AMR)

AF:

0.578

AC:

8829

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

2378

AN:

3472

East Asian (EAS)

AF:

0.583

AC:

2999

AN:

5148

South Asian (SAS)

AF:

0.490

AC:

2366

AN:

4828

European-Finnish (FIN)

AF:

0.611

AC:

6449

AN:

10556

Middle Eastern (MID)

AF:

0.702

AC:

205

AN:

292

European-Non Finnish (NFE)

AF:

0.652

AC:

44274

AN:

67918

Other (OTH)

AF:

0.659

AC:

1385

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1860

3720

5579

7439

9299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.642

Hom.:

3904

Bravo

AF:

0.635

Asia WGS

AF:

0.569

AC:

1976

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.99

(source)

DANN

Benign

0.29

PhyloP100

-0.48

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