3-126131662-G-A

Variant names:

• chr3-126131662-G-A
• rs2305225
• NM_012190.4:c.1473-128C>T

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1473-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,073,240 control chromosomes in the GnomAD database, including 206,300 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 (30659 hom., cov: 33)
  • Exomes 𝑓: 0.61 (175641 hom.)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 4 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=-0.9).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	NM_012190.4	MANE Select	c.1473-128C>T		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.1503-128C>T		intron	N/A	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.1170-128C>T		intron	N/A	NP_001257294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	ENST00000393434.7	TSL:1 MANE Select	c.1473-128C>T		intron	N/A	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.1503-128C>T		intron	N/A	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.1473-1369C>T		intron	N/A	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96314 AN: 151752 Hom.: 30644 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.615 AC: 566361 AN: 921370 Hom.: 175641 AF XY: 0.612 AC XY: 279568 AN XY: 457058

African (AFR) AF: 0.647 AC: 13375 AN: 20688

American (AMR) AF: 0.473 AC: 9803 AN: 20710

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 11012 AN: 16314

East Asian (EAS) AF: 0.565 AC: 18144 AN: 32106

South Asian (SAS) AF: 0.461 AC: 24701 AN: 53552

European-Finnish (FIN) AF: 0.612 AC: 20904 AN: 34178

Middle Eastern (MID) AF: 0.649 AC: 1838 AN: 2834

European-Non Finnish (NFE) AF: 0.630 AC: 441138 AN: 700028

Other (OTH) AF: 0.621 AC: 25446 AN: 40960

GnomAD4 genome AF: 0.635 AC: 96372 AN: 151870 Hom.: 30659 Cov.: 33 AF XY: 0.629 AC XY: 46681 AN XY: 74222

African (AFR) AF: 0.651 AC: 26954 AN: 41428

American (AMR) AF: 0.578 AC: 8834 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2375 AN: 3468

East Asian (EAS) AF: 0.582 AC: 2991 AN: 5140

South Asian (SAS) AF: 0.490 AC: 2360 AN: 4818

European-Finnish (FIN) AF: 0.612 AC: 6462 AN: 10554

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

European-Non Finnish (NFE) AF: 0.652 AC: 44245 AN: 67872

Other (OTH) AF: 0.659 AC: 1387 AN: 2104

Alfa AF: 0.641 Hom.: 10578

Bravo AF: 0.635

Asia WGS AF: 0.569 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.32
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: rs2305225; hg19: chr3-125850505;