3-126140524-T-C

Variant names:

• chr3-126140524-T-C
• rs11923466
• NM_012190.4:c.1077-2564A>G

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1077-2564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,908 control chromosomes in the GnomAD database, including 10,855 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 0.38 (10855 hom., cov: 32)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 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.1077-2564A>G		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.1107-2564A>G		intron	N/A	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.774-2564A>G		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.1077-2564A>G		intron	N/A	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.1107-2564A>G		intron	N/A	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.1077-2564A>G		intron	N/A	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57063 AN: 151790 Hom.: 10845 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.376 AC: 57103 AN: 151908 Hom.: 10855 Cov.: 32 AF XY: 0.373 AC XY: 27676 AN XY: 74258

African (AFR) AF: 0.305 AC: 12655 AN: 41482

American (AMR) AF: 0.391 AC: 5968 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1670 AN: 3462

East Asian (EAS) AF: 0.373 AC: 1933 AN: 5182

South Asian (SAS) AF: 0.380 AC: 1828 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3678 AN: 10536

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28050 AN: 67842

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.408 Hom.: 53269

Bravo AF: 0.377

Asia WGS AF: 0.398 AC: 1378 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.72
PhyloP100		-0.49
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: rs11923466; hg19: chr3-125859367; COSMIC: COSV56415470;