rs4964316

Positions:

• chr12-105039299-T-C

Variant summary

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

The NM_001034173.4(ALDH1L2):​c.2045+414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,156 control chromosomes in the GnomAD database, including 8,279 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 0.32 (8279 hom., cov: 33)
• Consequence: ALDH1L2 NM_001034173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1L2	NM_001034173.4	c.2045+414A>G		intron_variant		ENST00000258494.14
ALDH1L2	XM_047428406.1	c.1706+414A>G		intron_variant
ALDH1L2	XM_047428407.1	c.1607+414A>G		intron_variant
ALDH1L2	NR_027752.2	n.2063+414A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1L2	ENST00000258494.14	c.2045+414A>G		intron_variant		1	NM_001034173.4	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48047 AN: 152038 Hom.: 8279 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.316 AC: 48042 AN: 152156 Hom.: 8279 Cov.: 33 AF XY: 0.318 AC XY: 23657 AN XY: 74366

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.286

Alfa AF: 0.368 Hom.: 21239

Bravo AF: 0.303

Asia WGS AF: 0.358 AC: 1245 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4964316; hg19: chr12-105433077;