3-126155545-C-T

Variant names:

• chr3-126155545-C-T
• rs2276731
• NM_012190.4:c.529-42G>A

Variant summary

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

The NM_012190.4(ALDH1L1):​c.529-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,554,482 control chromosomes in the GnomAD database, including 521,284 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 0.83 (52032 hom., cov: 33)
  • Exomes 𝑓: 0.82 (469252 hom.)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.529-42G>A		intron_variant	Intron 4 of 22	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.529-42G>A		intron_variant	Intron 4 of 22	1	NM_012190.4	ENSP00000377083.3

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125678 AN: 152046 Hom.: 51988 Cov.: 33

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.803

GnomAD3 exomes AF: 0.832 AC: 177292 AN: 213166 Hom.: 73799 AF XY: 0.834 AC XY: 95553 AN XY: 114608

Gnomad AFR exome AF: 0.847

Gnomad AMR exome AF: 0.844

Gnomad ASJ exome AF: 0.844

Gnomad EAS exome AF: 0.749

Gnomad SAS exome AF: 0.899

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.815

Gnomad OTH exome AF: 0.827

GnomAD4 exome AF: 0.817 AC: 1146022 AN: 1402318 Hom.: 469252 Cov.: 22 AF XY: 0.820 AC XY: 570686 AN XY: 696232

Gnomad4 AFR exome AF: 0.859

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.839

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.899

Gnomad4 FIN exome AF: 0.870

Gnomad4 NFE exome AF: 0.810

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.827 AC: 125778 AN: 152164 Hom.: 52032 Cov.: 33 AF XY: 0.829 AC XY: 61683 AN XY: 74382

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.801

Alfa AF: 0.824 Hom.: 26740

Bravo AF: 0.822

Asia WGS AF: 0.818 AC: 2845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2276731; hg19: chr3-125874388;