dbSNP rs4964316: ALDH1L2:c.2045+414A>G (chr12-105039299-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_001034173.4(ALDH1L2):c.2045+414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,156 control chromosomes in the GnomAD database, including 8,279 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 0.32 ( 8279 hom., cov: 33)

Consequence

ALDH1L2
NM_001034173.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0600

Publications

5 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

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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 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.2045+414A>G		intron	N/A	NP_001029345.2
	ALDH1L2	NR_027752.2		n.2063+414A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ALDH1L2	ENST00000258494.14	TSL:1 MANE Select	c.2045+414A>G	intron	N/A	ENSP00000258494.9
ALDH1L2	ENST00000652515.1		c.2072+414A>G	intron	N/A	ENSP00000499136.1
ALDH1L2	ENST00000890520.1		c.2045+414A>G	intron	N/A	ENSP00000560579.1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48047

AN:

152038

Hom.:

8279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.288

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

GnomAD4 genome

AF:

0.316

AC:

48042

AN:

152156

Hom.:

8279

Cov.:

AF XY:

0.318

AC XY:

23657

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.181

AC:

7508

AN:

41532

American (AMR)

AF:

0.339

AC:

5182

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1069

AN:

3470

East Asian (EAS)

AF:

0.256

AC:

1327

AN:

5188

South Asian (SAS)

AF:

0.506

AC:

2437

AN:

4812

European-Finnish (FIN)

AF:

0.348

AC:

3671

AN:

10542

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.379

AC:

25785

AN:

68004

Other (OTH)

AF:

0.286

AC:

602

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1641

3282

4922

6563

8204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.357

Hom.:

31289

Bravo

AF:

0.303

Asia WGS

AF:

0.358

AC:

1245

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.1

(source)

DANN

Benign

0.78

PhyloP100

0.060

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over