rs2069033

Variant names:

• chr3-126133795-C-A
• rs2069033
• NM_012190.4:c.1472+1740G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-126133795-C-A
• chr3-126133795-C-G

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1472+1740G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,026 control chromosomes in the GnomAD database, including 14,558 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 0.43 (14558 hom., cov: 33)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 2 publications found

Genes affected

ALDH1L1 (HGNC:3978): (aldehyde dehydrogenase 1 family member L1) The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1472+1740G>T		intron_variant	Intron 12 of 22	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1472+1740G>T		intron_variant	Intron 12 of 22	1	NM_012190.4	ENSP00000377083.3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65542 AN: 151908 Hom.: 14555 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.431 AC: 65573 AN: 152026 Hom.: 14558 Cov.: 33 AF XY: 0.430 AC XY: 31948 AN XY: 74308

African (AFR) AF: 0.318 AC: 13185 AN: 41482

American (AMR) AF: 0.444 AC: 6788 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1899 AN: 5146

South Asian (SAS) AF: 0.390 AC: 1881 AN: 4822

European-Finnish (FIN) AF: 0.494 AC: 5224 AN: 10570

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.490 AC: 33257 AN: 67930

Other (OTH) AF: 0.446 AC: 941 AN: 2110

Alfa AF: 0.464 Hom.: 2162

Bravo AF: 0.424

Asia WGS AF: 0.395 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		0.20
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: rs2069033; hg19: chr3-125852638;