rs10861342

Variant names:

• chr12-105065019-T-C
• rs10861342
• NM_001034173.4:c.786+248A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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]

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ALDH1L2	NM_001034173.4	c.786+248A>G		intron_variant	Intron 6 of 22	ENST00000258494.14	NP_001029345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L2	ENST00000258494.14	c.786+248A>G		intron_variant	Intron 6 of 22	1	NM_001034173.4	ENSP00000258494.9

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

African (AFR) AF: 0.0707 AC: 2935 AN: 41528

American (AMR) AF: 0.139 AC: 2126 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3466

East Asian (EAS) AF: 0.236 AC: 1217 AN: 5158

South Asian (SAS) AF: 0.143 AC: 690 AN: 4822

European-Finnish (FIN) AF: 0.0865 AC: 917 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6306 AN: 68004

Other (OTH) AF: 0.0868 AC: 183 AN: 2108

Alfa AF: 0.0940 Hom.: 1587

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
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10861342; hg19: chr12-105458797;