chr12-105058664-G-A

Variant names:

• chr12-105058664-G-A
• rs10861337
• NM_001034173.4:c.1140-444C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L2	NM_001034173.4	MANE Select	c.1140-444C>T		intron	N/A	NP_001029345.2
	ALDH1L2	NR_027752.2		n.1158-444C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L2	ENST00000258494.14	TSL:1 MANE Select	c.1140-444C>T		intron	N/A	ENSP00000258494.9
	ALDH1L2	ENST00000652515.1		c.1167-444C>T		intron	N/A	ENSP00000499136.1
	NOPCHAP1	ENST00000622317.5	TSL:5	c.*31-1767G>A		intron	N/A	ENSP00000477543.2

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

African (AFR) AF: 0.0751 AC: 3119 AN: 41534

American (AMR) AF: 0.139 AC: 2126 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.235 AC: 1218 AN: 5174

South Asian (SAS) AF: 0.144 AC: 692 AN: 4818

European-Finnish (FIN) AF: 0.0864 AC: 914 AN: 10578

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

European-Non Finnish (NFE) AF: 0.0927 AC: 6303 AN: 68016

Other (OTH) AF: 0.0881 AC: 186 AN: 2112

Alfa AF: 0.0961 Hom.: 1130

Bravo AF: 0.0985

Asia WGS AF: 0.198 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.62
PhyloP100		-0.58
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: rs10861337; hg19: chr12-105452442; COSMIC: COSV51555975;