Genetic Variant ALDH1L1:c.127+623A>G (chr3-126160230-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.127+623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,054 control chromosomes in the GnomAD database, including 33,495 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 0.66 ( 33495 hom., cov: 33)

Exomes 𝑓: 0.64 ( 126 hom. )

Failed GnomAD Quality Control

Consequence

ALDH1L1
NM_012190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.710

Publications

5 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:

LOC105374083 (HGNC:):

LOC105374083 links:

RNU1-30P (HGNC:48372): (RNA, U1 small nuclear 30, pseudogene)

RNU1-30P 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=-0.97).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4 link	c.127+623A>G		intron_variant	Intron 2 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.127+623A>G		intron_variant	Intron 2 of 22	1	NM_012190.4	ENSP00000377083.3		O75891-1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100746

AN:

151936

Hom.:

33482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.681

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.685

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.637

AC:

396

AN:

622

Hom.:

126

AF XY:

0.634

AC XY:

203

AN XY:

320

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.641

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.636

AC:

327

AN:

514

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.663

AC:

100810

AN:

152054

Hom.:

33495

Cov.:

AF XY:

0.661

AC XY:

49108

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.671

AC:

27806

AN:

41462

American (AMR)

AF:

0.680

AC:

10408

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2200

AN:

3466

East Asian (EAS)

AF:

0.655

AC:

3381

AN:

5158

South Asian (SAS)

AF:

0.604

AC:

2909

AN:

4818

European-Finnish (FIN)

AF:

0.596

AC:

6303

AN:

10570

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.670

AC:

45513

AN:

67966

Other (OTH)

AF:

0.684

AC:

1444

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1781

3562

5342

7123

8904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.663

Hom.:

12758

Bravo

AF:

0.670

Asia WGS

AF:

0.625

AC:

2178

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.6

(source)

DANN

Benign

0.72

PhyloP100

-0.71

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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3-126160230-T-C

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