3-126112174-C-T

Variant names:

• chr3-126112174-C-T
• rs3772424
• NM_012190.4:c.2181+608G>A

Variant summary

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

The NM_001270364.2(ALDH1L1):​c.2211+608G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,130 control chromosomes in the GnomAD database, including 3,385 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 0.21 (3385 hom., cov: 33)
• Consequence: ALDH1L1 NM_001270364.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270364.2. 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.2181+608G>A		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.2211+608G>A		intron	N/A	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.1878+608G>A		intron	N/A	NP_001257294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	ENST00000393434.7	TSL:1 MANE Select	c.2181+608G>A		intron	N/A	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.2211+608G>A		intron	N/A	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.*412+608G>A		intron	N/A	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31850 AN: 152012 Hom.: 3378 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31875 AN: 152130 Hom.: 3385 Cov.: 33 AF XY: 0.212 AC XY: 15746 AN XY: 74358

African (AFR) AF: 0.204 AC: 8481 AN: 41504

American (AMR) AF: 0.192 AC: 2937 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1025 AN: 5172

South Asian (SAS) AF: 0.133 AC: 643 AN: 4826

European-Finnish (FIN) AF: 0.288 AC: 3046 AN: 10562

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14539 AN: 67986

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.204 Hom.: 9104

Bravo AF: 0.201

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.82
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3772424; hg19: chr3-125831017;