rs6774437

Variant names:

• chr3-126120147-A-C
• rs6774437
• NM_012190.4:c.1889-2049T>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.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
• Publications: 3 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=-0.82).
• 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 rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1889-2049T>G		intron_variant	Intron 16 of 22	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1889-2049T>G		intron_variant	Intron 16 of 22	1	NM_012190.4	ENSP00000377083.3

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

African (AFR) AF: 0.382 AC: 15839 AN: 41474

American (AMR) AF: 0.438 AC: 6701 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3472

East Asian (EAS) AF: 0.533 AC: 2760 AN: 5176

South Asian (SAS) AF: 0.434 AC: 2088 AN: 4816

European-Finnish (FIN) AF: 0.545 AC: 5767 AN: 10586

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36126 AN: 67986

Other (OTH) AF: 0.489 AC: 1033 AN: 2112

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
PhyloP100		0.014
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: rs6774437; hg19: chr3-125838990; COSMIC: COSV56410795; COSMIC: COSV56410795;