rs10861342

Positions:

• chr12-105065019-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034173.4(ALDH1L2):​c.786+248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,182 control chromosomes in the GnomAD database, including 818 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 0.096 (818 hom., cov: 31)
• Consequence: ALDH1L2 NM_001034173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1L2	NM_001034173.4	c.786+248A>G		intron_variant		ENST00000258494.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1L2	ENST00000258494.14	c.786+248A>G		intron_variant		1	NM_001034173.4	P1

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14535 AN: 152066 Hom.: 816 Cov.: 31

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.0853

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

GnomAD4 genome AF: 0.0957 AC: 14564 AN: 152182 Hom.: 818 Cov.: 31 AF XY: 0.0993 AC XY: 7388 AN XY: 74392

Gnomad4 AFR AF: 0.0707

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0865

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.0868

Alfa AF: 0.0937 Hom.: 1007

Bravo AF: 0.0973

Asia WGS AF: 0.196 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs10861342; hg19: chr12-105458797;