rs10934751

chr3-126149670-A-Gchr3-126149670-A-T

Variant summary

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

The NM_012190.4(ALDH1L1):c.984+736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,044 control chromosomes in the GnomAD database, including 14,047 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 0.42 (14047 hom., cov: 33)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1L1	NM_012190.4	c.984+736T>C		intron_variant		ENST00000393434.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.984+736T>C		intron_variant		1	NM_012190.4	P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64043 AN: 151926 Hom.: 14039 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.421 AC: 64076 AN: 152044 Hom.: 14047 Cov.: 33 AF XY: 0.418 AC XY: 31087 AN XY: 74312

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.469

Alfa AF: 0.476 Hom.: 27943

Bravo AF: 0.421

Asia WGS AF: 0.507 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.3
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10934751; hg19: chr3-125868513;