3-126128278-T-C

Position:

• chr3-126128278-T-C

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1694+1945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,132 control chromosomes in the GnomAD database, including 30,903 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 0.64 (30872 hom., cov: 32)
  • Exomes 𝑓: 0.69 (31 hom.)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1694+1945A>G		intron_variant		ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1694+1945A>G		intron_variant		1	NM_012190.4	ENSP00000377083.3

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96660 AN: 151882 Hom.: 30857 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.660

GnomAD4 exome AF: 0.689 AC: 91 AN: 132 Hom.: 31 AF XY: 0.720 AC XY: 72 AN XY: 100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.736

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.636 AC: 96719 AN: 152000 Hom.: 30872 Cov.: 32 AF XY: 0.631 AC XY: 46856 AN XY: 74300

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.662

Alfa AF: 0.645 Hom.: 41062

Bravo AF: 0.636

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	-0.98
CADD	Benign	3.1
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: rs2365004; hg19: chr3-125847121;