rs2290053

Positions:

• chr3-126114417-C-T

Variant summary

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

The NM_012190.4(ALDH1L1):​c.2082+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 581,716 control chromosomes in the GnomAD database, including 64,042 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 0.47 (16891 hom., cov: 33)
  • Exomes 𝑓: 0.46 (47151 hom.)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.2082+140G>A		intron_variant		ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.2082+140G>A		intron_variant		1	NM_012190.4	ENSP00000377083	P1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71463 AN: 151908 Hom.: 16874 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.462 AC: 198718 AN: 429688 Hom.: 47151 AF XY: 0.463 AC XY: 99398 AN XY: 214852

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.470 AC: 71518 AN: 152028 Hom.: 16891 Cov.: 33 AF XY: 0.465 AC XY: 34563 AN XY: 74304

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.470

Alfa AF: 0.484 Hom.: 36706

Bravo AF: 0.465

Asia WGS AF: 0.419 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.78

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: rs2290053; hg19: chr3-125833260; COSMIC: COSV56416292; COSMIC: COSV56416292;