rs6774437

chr3-126120147-A-C

Variant summary

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

The NM_012190.4(ALDH1L1):c.1889-2049T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,108 control chromosomes in the GnomAD database, including 17,747 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 0.48 (17747 hom., cov: 34)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1L1	NM_012190.4	c.1889-2049T>G		intron_variant		ENST00000393434.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1889-2049T>G		intron_variant		1	NM_012190.4	P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72717 AN: 151988 Hom.: 17740 Cov.: 34

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.478 AC: 72753 AN: 152108 Hom.: 17747 Cov.: 34 AF XY: 0.477 AC XY: 35439 AN XY: 74360

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.489

Alfa AF: 0.506 Hom.: 2466

Bravo AF: 0.466

Asia WGS AF: 0.515 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.5
Dann	Benign	0.77

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: rs6774437; hg19: chr3-125838990; COSMIC: COSV56410795; COSMIC: COSV56410795;