3-126160613-T-C

Variant names:

• chr3-126160613-T-C
• rs4646701
• NM_012190.4:c.127+240A>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.127+240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,114 control chromosomes in the GnomAD database, including 22,755 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 0.54 (22755 hom., cov: 33)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• 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]

LOC105374083 (HGNC:):

RNU1-30P (HGNC:48372): (RNA, U1 small nuclear 30, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 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.127+240A>G		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.157+240A>G		intron	N/A	NP_001257293.1	O75891-3
	ALDH1L1	NM_001270365.2		c.127+240A>G		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.127+240A>G		intron	N/A	ENSP00000377083.3	O75891-1
	ALDH1L1	ENST00000273450.7	TSL:1	c.157+240A>G		intron	N/A	ENSP00000273450.3	O75891-3
	ALDH1L1	ENST00000393431.6	TSL:1	c.127+240A>G		intron	N/A	ENSP00000377081.2	O75891-4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82171 AN: 151996 Hom.: 22756 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.540 AC: 82190 AN: 152114 Hom.: 22755 Cov.: 33 AF XY: 0.536 AC XY: 39824 AN XY: 74342

African (AFR) AF: 0.443 AC: 18376 AN: 41510

American (AMR) AF: 0.507 AC: 7753 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2382 AN: 5166

South Asian (SAS) AF: 0.553 AC: 2662 AN: 4816

European-Finnish (FIN) AF: 0.518 AC: 5475 AN: 10564

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41516 AN: 67966

Other (OTH) AF: 0.573 AC: 1212 AN: 2114

Alfa AF: 0.587 Hom.: 32660

Bravo AF: 0.537

Asia WGS AF: 0.486 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.56
PhyloP100		-0.046
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: rs4646701; hg19: chr3-125879456;