rs2002287

Positions:

• chr3-126130395-G-A
• chr3-126130395-G-T

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1624-102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,066,462 control chromosomes in the GnomAD database, including 217,628 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 0.63 (30780 hom., cov: 34)
  • Exomes 𝑓: 0.64 (186848 hom.)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

ALDH1L1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1624-102C>T		intron_variant		ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1624-102C>T		intron_variant		1	NM_012190.4	ENSP00000377083.3

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96550 AN: 152038 Hom.: 30765 Cov.: 34

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.635 AC: 580769 AN: 914306 Hom.: 186848 AF XY: 0.633 AC XY: 286313 AN XY: 452618

Gnomad4 AFR exome AF: 0.654

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.619

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.636

GnomAD4 genome AF: 0.635 AC: 96608 AN: 152156 Hom.: 30780 Cov.: 34 AF XY: 0.629 AC XY: 46807 AN XY: 74366

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.660

Alfa AF: 0.563 Hom.: 2898

Bravo AF: 0.635

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.53

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: rs2002287; hg19: chr3-125849238;