chr3-126147183-A-G

Position:

• chr3-126147183-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012190.4(ALDH1L1):​c.985-257T>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_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1L1	NM_012190.4	c.985-257T>C		intron_variant		ENST00000393434.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.985-257T>C		intron_variant		1	NM_012190.4	P1

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

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.681

Alfa AF: 0.602 Hom.: 54258

Bravo AF: 0.694

Asia WGS AF: 0.605 AC: 2099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1965848; hg19: chr3-125866026;