rs10861337

Positions:

• chr12-105058664-G-A

Variant summary

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

The NM_001034173.4(ALDH1L2):​c.1140-444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 152,200 control chromosomes in the GnomAD database, including 828 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 0.097 (828 hom., cov: 32)
• Consequence: ALDH1L2 NM_001034173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L2	NM_001034173.4	c.1140-444C>T		intron_variant		ENST00000258494.14	NP_001029345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L2	ENST00000258494.14	c.1140-444C>T		intron_variant		1	NM_001034173.4	ENSP00000258494	P1

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14711 AN: 152082 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.0746

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: 0.0864

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.0871

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

GnomAD4 genome AF: 0.0969 AC: 14748 AN: 152200 Hom.: 828 Cov.: 32 AF XY: 0.101 AC XY: 7490 AN XY: 74414

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.0916 Hom.: 73

Bravo AF: 0.0985

Asia WGS AF: 0.198 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.62

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: rs10861337; hg19: chr12-105452442; COSMIC: COSV51555975;