12-105034586-T-G

Variant names:

• chr12-105034586-T-G
• rs4281549
• NM_001034173.4:c.2146-188A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034173.4(ALDH1L2):​c.2146-188A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,078 control chromosomes in the GnomAD database, including 5,394 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 0.23 (5394 hom., cov: 32)
• Consequence: ALDH1L2 NM_001034173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L2	NM_001034173.4	c.2146-188A>C		intron_variant	Intron 18 of 22	ENST00000258494.14	NP_001029345.2
ALDH1L2	XM_047428406.1	c.1807-188A>C		intron_variant	Intron 18 of 22		XP_047284362.1
ALDH1L2	XM_047428407.1	c.1708-188A>C		intron_variant	Intron 17 of 21		XP_047284363.1
ALDH1L2	NR_027752.2	n.2164-188A>C		intron_variant	Intron 18 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L2	ENST00000258494.14	c.2146-188A>C		intron_variant	Intron 18 of 22	1	NM_001034173.4	ENSP00000258494.9

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34400 AN: 151960 Hom.: 5385 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.227 AC: 34459 AN: 152078 Hom.: 5394 Cov.: 32 AF XY: 0.228 AC XY: 16962 AN XY: 74338

African (AFR) AF: 0.421 AC: 17440 AN: 41436

American (AMR) AF: 0.150 AC: 2285 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2582 AN: 5174

South Asian (SAS) AF: 0.170 AC: 819 AN: 4822

European-Finnish (FIN) AF: 0.187 AC: 1974 AN: 10584

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8403 AN: 67990

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.184 Hom.: 466

Bravo AF: 0.236

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.1
DANN	Benign	0.65
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

Publications

LitVar

Other links and lift over

dbSNP: rs4281549; hg19: chr12-105428364;