12-105094491-T-C

Variant names:

• chr12-105094491-T-C
• rs1196885
• ENST00000652515.1:c.75+12297A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652515.1(ALDH1L2):​c.75+12297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.87 (54462 hom., cov: 19)
• Consequence: ALDH1L2 ENST00000652515.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L2	ENST00000652515.1	c.75+12297A>G		intron_variant	Intron 1 of 22			ENSP00000499136.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 124137 AN: 142392 Hom.: 54411 Cov.: 19

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.872 AC: 124236 AN: 142490 Hom.: 54462 Cov.: 19 AF XY: 0.876 AC XY: 60022 AN XY: 68486

African (AFR) AF: 0.938 AC: 35328 AN: 37674

American (AMR) AF: 0.899 AC: 12668 AN: 14096

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3069 AN: 3442

East Asian (EAS) AF: 0.999 AC: 4836 AN: 4842

South Asian (SAS) AF: 0.946 AC: 4189 AN: 4430

European-Finnish (FIN) AF: 0.847 AC: 6927 AN: 8178

Middle Eastern (MID) AF: 0.905 AC: 257 AN: 284

European-Non Finnish (NFE) AF: 0.817 AC: 54501 AN: 66680

Other (OTH) AF: 0.870 AC: 1720 AN: 1976

Alfa AF: 0.844 Hom.: 5594

Bravo AF: 0.879

Asia WGS AF: 0.963 AC: 3349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.15
PhyloP100		-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1196885; hg19: chr12-105488269;