rs4646701

Positions:

• chr3-126160613-T-C
• chr3-126160613-T-G

Variant summary

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

The NM_012190.4(ALDH1L1):​c.127+240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,114 control chromosomes in the GnomAD database, including 22,755 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 0.54 (22755 hom., cov: 33)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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]

LOC105374083 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1L1	NM_012190.4	c.127+240A>G		intron_variant		ENST00000393434.7
LOC105374083	XR_007096056.1	n.246+176T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.127+240A>G		intron_variant		1	NM_012190.4	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82171 AN: 151996 Hom.: 22756 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.540 AC: 82190 AN: 152114 Hom.: 22755 Cov.: 33 AF XY: 0.536 AC XY: 39824 AN XY: 74342

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.573

Alfa AF: 0.594 Hom.: 25343

Bravo AF: 0.537

Asia WGS AF: 0.486 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.56

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: rs4646701; hg19: chr3-125879456;