chr3-126140524-T-C

Position:

• chr3-126140524-T-C

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1077-2564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,908 control chromosomes in the GnomAD database, including 10,855 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 0.38 (10855 hom., cov: 32)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1077-2564A>G		intron_variant		ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1077-2564A>G		intron_variant		1	NM_012190.4	ENSP00000377083	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57063 AN: 151790 Hom.: 10845 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.376 AC: 57103 AN: 151908 Hom.: 10855 Cov.: 32 AF XY: 0.373 AC XY: 27676 AN XY: 74258

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.397

Alfa AF: 0.416 Hom.: 26530

Bravo AF: 0.377

Asia WGS AF: 0.398 AC: 1378 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.72

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: rs11923466; hg19: chr3-125859367; COSMIC: COSV56415470;