3-126131258-C-T

Variant names:

• chr3-126131258-C-T
• rs4646733
• NM_012190.4:c.1623+126G>A

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1623+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,226,954 control chromosomes in the GnomAD database, including 236,281 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 (30669 hom., cov: 34)
  • Exomes 𝑓: 0.61 (205612 hom.)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	NM_012190.4	MANE Select	c.1623+126G>A		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.1653+126G>A		intron	N/A	NP_001257293.1	O75891-3
	ALDH1L1	NM_001270365.2		c.1320+126G>A		intron	N/A	NP_001257294.1	O75891-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	ENST00000393434.7	TSL:1 MANE Select	c.1623+126G>A		intron	N/A	ENSP00000377083.3	O75891-1
	ALDH1L1	ENST00000273450.7	TSL:1	c.1653+126G>A		intron	N/A	ENSP00000273450.3	O75891-3
	ALDH1L1	ENST00000393431.6	TSL:1	c.1473-965G>A		intron	N/A	ENSP00000377081.2	O75891-4

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96343 AN: 151818 Hom.: 30654 Cov.: 34

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.614 AC: 660232 AN: 1075018 Hom.: 205612 AF XY: 0.611 AC XY: 322959 AN XY: 528262

African (AFR) AF: 0.639 AC: 15366 AN: 24032

American (AMR) AF: 0.429 AC: 10840 AN: 25256

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 10692 AN: 16142

East Asian (EAS) AF: 0.557 AC: 18769 AN: 33696

South Asian (SAS) AF: 0.413 AC: 19849 AN: 48036

European-Finnish (FIN) AF: 0.603 AC: 25512 AN: 42320

Middle Eastern (MID) AF: 0.650 AC: 2546 AN: 3916

European-Non Finnish (NFE) AF: 0.632 AC: 529363 AN: 837158

Other (OTH) AF: 0.614 AC: 27295 AN: 44462

GnomAD4 genome AF: 0.634 AC: 96401 AN: 151936 Hom.: 30669 Cov.: 34 AF XY: 0.629 AC XY: 46682 AN XY: 74248

African (AFR) AF: 0.651 AC: 26957 AN: 41426

American (AMR) AF: 0.578 AC: 8829 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2378 AN: 3472

East Asian (EAS) AF: 0.583 AC: 2999 AN: 5148

South Asian (SAS) AF: 0.490 AC: 2366 AN: 4828

European-Finnish (FIN) AF: 0.611 AC: 6449 AN: 10556

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 44274 AN: 67918

Other (OTH) AF: 0.659 AC: 1385 AN: 2102

Alfa AF: 0.642 Hom.: 3904

Bravo AF: 0.635

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.99
DANN	Benign	0.29
PhyloP100		-0.48
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: rs4646733; hg19: chr3-125850101;