rs10861340

Variant names:

• chr12-105060319-A-G
• rs10861340
• NM_001034173.4:c.1139+662T>C

Variant summary

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

The NM_001034173.4(ALDH1L2):​c.1139+662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,058 control chromosomes in the GnomAD database, including 6,867 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 0.28 (6867 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ALDH1L2 NM_001034173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L2	NM_001034173.4	c.1139+662T>C		intron_variant	Intron 9 of 22	ENST00000258494.14	NP_001029345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L2	ENST00000258494.14	c.1139+662T>C		intron_variant	Intron 9 of 22	1	NM_001034173.4	ENSP00000258494.9

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41899 AN: 151940 Hom.: 6853 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.276 AC: 41978 AN: 152058 Hom.: 6867 Cov.: 32 AF XY: 0.274 AC XY: 20405 AN XY: 74360

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.233

Alfa AF: 0.248 Hom.: 1450

Bravo AF: 0.289

Asia WGS AF: 0.311 AC: 1082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.5
DANN	Benign	0.87

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: rs10861340; hg19: chr12-105454097;