3-126160230-T-C

Position:

• chr3-126160230-T-C

Variant summary

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

The ENST00000393434.7(ALDH1L1):​c.127+623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,054 control chromosomes in the GnomAD database, including 33,495 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 0.66 (33495 hom., cov: 33)
  • Exomes 𝑓: 0.64 (126 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALDH1L1 ENST00000393434.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.127+623A>G		intron_variant		ENST00000393434.7	NP_036322.2
LOC105374083	XR_007096056.1	n.93+55T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.127+623A>G		intron_variant		1	NM_012190.4	ENSP00000377083	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100746 AN: 151936 Hom.: 33482 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.685

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.637 AC: 396 AN: 622 Hom.: 126 AF XY: 0.634 AC XY: 203 AN XY: 320

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.750

Gnomad4 NFE exome AF: 0.636

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.663 AC: 100810 AN: 152054 Hom.: 33495 Cov.: 33 AF XY: 0.661 AC XY: 49108 AN XY: 74344

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.684

Alfa AF: 0.661 Hom.: 7893

Bravo AF: 0.670

Asia WGS AF: 0.625 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
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: rs1823213; hg19: chr3-125879073;