3-126147183-A-G

Variant names:

• chr3-126147183-A-G
• rs1965848
• NM_012190.4:c.985-257T>C

Variant summary

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

The NM_001270364.2(ALDH1L1):​c.1015-257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,008 control chromosomes in the GnomAD database, including 35,873 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 0.67 (35873 hom., cov: 32)
• Consequence: ALDH1L1 NM_001270364.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	NM_012190.4	MANE Select	c.985-257T>C		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.1015-257T>C		intron	N/A	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.682-257T>C		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.985-257T>C		intron	N/A	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.1015-257T>C		intron	N/A	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.985-257T>C		intron	N/A	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101921 AN: 151890 Hom.: 35810 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.671 AC: 102046 AN: 152008 Hom.: 35873 Cov.: 32 AF XY: 0.662 AC XY: 49191 AN XY: 74272

African (AFR) AF: 0.900 AC: 37359 AN: 41516

American (AMR) AF: 0.652 AC: 9954 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2222 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3061 AN: 5132

South Asian (SAS) AF: 0.494 AC: 2372 AN: 4804

European-Finnish (FIN) AF: 0.492 AC: 5201 AN: 10564

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39746 AN: 67926

Other (OTH) AF: 0.681 AC: 1440 AN: 2114

Alfa AF: 0.619 Hom.: 90706

Bravo AF: 0.694

Asia WGS AF: 0.605 AC: 2099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.58
PhyloP100		-0.25
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: rs1965848; hg19: chr3-125866026;