Genetic Variant ALDH1L1:c.1694+1945A>G (chr3-126128278-T-C) – 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.1694+1945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,132 control chromosomes in the GnomAD database, including 30,903 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 0.64 ( 30872 hom., cov: 32)

Exomes 𝑓: 0.69 ( 31 hom. )

Consequence

ALDH1L1
NM_012190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.834

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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4 link	c.1694+1945A>G		intron_variant	Intron 14 of 22	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7 link	c.1694+1945A>G		intron_variant	Intron 14 of 22	1	NM_012190.4	ENSP00000377083.3

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96660

AN:

151882

Hom.:

30857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.584

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.660

GnomAD4 exome

AF:

0.689

AC:

AN:

132

Hom.:

AF XY:

0.720

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.600

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.736

AC:

AN:

106

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.636

AC:

96719

AN:

152000

Hom.:

30872

Cov.:

AF XY:

0.631

AC XY:

46856

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.654

AC:

27127

AN:

41460

American (AMR)

AF:

0.578

AC:

8838

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

2377

AN:

3470

East Asian (EAS)

AF:

0.584

AC:

3005

AN:

5148

South Asian (SAS)

AF:

0.491

AC:

2360

AN:

4810

European-Finnish (FIN)

AF:

0.613

AC:

6482

AN:

10578

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.653

AC:

44359

AN:

67938

Other (OTH)

AF:

0.662

AC:

1399

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1826

3652

5477

7303

9129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.645

Hom.:

52291

Bravo

AF:

0.636

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

-0.98

CADD

Benign

3.1

(source)

DANN

Benign

0.78

PhyloP100

-0.83

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