dbSNP rs2002287: ALDH1L1:c.1624-102C>T (chr3-126130395-G-A) – 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.1624-102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,066,462 control chromosomes in the GnomAD database, including 217,628 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 ( 30780 hom., cov: 34)

Exomes 𝑓: 0.64 ( 186848 hom. )

Consequence

ALDH1L1
NM_012190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

13 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=-0.94).

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.1624-102C>T		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.1624-102C>T		intron_variant	Intron 13 of 22	1	NM_012190.4	ENSP00000377083.3		O75891-1

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96550

AN:

152038

Hom.:

30765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.658

GnomAD4 exome

AF:

0.635

AC:

580769

AN:

914306

Hom.:

186848

AF XY:

0.633

AC XY:

286313

AN XY:

452618

show subpopulations

African (AFR)

AF:

0.654

AC:

12918

AN:

19742

American (AMR)

AF:

0.480

AC:

7533

AN:

15700

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

10254

AN:

14958

East Asian (EAS)

AF:

0.570

AC:

16201

AN:

28422

South Asian (SAS)

AF:

0.478

AC:

19841

AN:

41514

European-Finnish (FIN)

AF:

0.619

AC:

25342

AN:

40926

Middle Eastern (MID)

AF:

0.695

AC:

2989

AN:

4302

European-Non Finnish (NFE)

AF:

0.649

AC:

460556

AN:

709214

Other (OTH)

AF:

0.636

AC:

25135

AN:

39528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

9894

19788

29683

39577

49471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11718

23436

35154

46872

58590

<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:

0.635

AC:

96608

AN:

152156

Hom.:

30780

Cov.:

AF XY:

0.629

AC XY:

46807

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.652

AC:

27051

AN:

41518

American (AMR)

AF:

0.578

AC:

8841

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

2378

AN:

3472

East Asian (EAS)

AF:

0.582

AC:

3004

AN:

5160

South Asian (SAS)

AF:

0.490

AC:

2359

AN:

4818

European-Finnish (FIN)

AF:

0.613

AC:

6493

AN:

10592

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.652

AC:

44322

AN:

67982

Other (OTH)

AF:

0.660

AC:

1392

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1887

3774

5660

7547

9434

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:

0.567

Hom.:

3063

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

-0.94

CADD

Benign

0.13

(source)

DANN

Benign

0.53

PhyloP100

-1.3

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