Genetic Variant ALDH1L2:c.2146-188A>C (chr12-105034586-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001034173.4(ALDH1L2):c.2146-188A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,078 control chromosomes in the GnomAD database, including 5,394 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 0.23 ( 5394 hom., cov: 32)

Consequence

ALDH1L2
NM_001034173.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138

Publications

4 publications found

Variant links:

Genes affected

ALDH1L2 (HGNC:26777): (aldehyde dehydrogenase 1 family member L2) This gene encodes a member of both the aldehyde dehydrogenase superfamily and the formyl transferase superfamily. This member is the mitochondrial form of 10-formyltetrahydrofolate dehydrogenase (FDH), which converts 10-formyltetrahydrofolate to tetrahydrofolate and CO2 in an NADP(+)-dependent reaction, and plays an essential role in the distribution of one-carbon groups between the cytosolic and mitochondrial compartments of the cell. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

ALDH1L2 links:

NOPCHAP1 (HGNC:28628): (NOP protein chaperone 1) Enables box C/D snoRNP complex binding activity. Involved in box C/D snoRNP assembly. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NOPCHAP1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001034173.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034173.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L2	NM_001034173.4	MANE Select	c.2146-188A>C		intron	N/A	NP_001029345.2	Q3SY69-1
	ALDH1L2	NR_027752.2		n.2164-188A>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH1L2	ENST00000258494.14	TSL:1 MANE Select	c.2146-188A>C	intron	N/A	ENSP00000258494.9	Q3SY69-1
ALDH1L2	ENST00000652515.1		c.2173-188A>C	intron	N/A	ENSP00000499136.1	A0A494C1M4
ALDH1L2	ENST00000890520.1		c.2146-2652A>C	intron	N/A	ENSP00000560579.1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34400

AN:

151960

Hom.:

5385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.227

AC:

34459

AN:

152078

Hom.:

5394

Cov.:

AF XY:

0.228

AC XY:

16962

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.421

AC:

17440

AN:

41436

American (AMR)

AF:

0.150

AC:

2285

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

377

AN:

3472

East Asian (EAS)

AF:

0.499

AC:

2582

AN:

5174

South Asian (SAS)

AF:

0.170

AC:

819

AN:

4822

European-Finnish (FIN)

AF:

0.187

AC:

1974

AN:

10584

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8403

AN:

67990

Other (OTH)

AF:

0.201

AC:

425

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1217

2434

3651

4868

6085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.184

Hom.:

466

Bravo

AF:

0.236

Asia WGS

AF:

0.334

AC:

1160

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.1

(source)

DANN

Benign

0.65

PhyloP100

0.14

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over