chr3-126185322-A-G

Position:

• chr3-126185322-A-G

Variant summary

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

The NR_046383.1(ALDH1L1-AS2):​n.480+4778A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,084 control chromosomes in the GnomAD database, including 19,135 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 0.50 (19135 hom., cov: 33)
• Consequence: ALDH1L1-AS2 NR_046383.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

Genes affected

ALDH1L1-AS2 (HGNC:42446): (ALDH1L1 antisense RNA 2)

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1-AS2	NR_046383.1	n.480+4778A>G		intron_variant, non_coding_transcript_variant
ALDH1L1	XM_024453325.2	c.-24+12413T>C		intron_variant			XP_024309093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1-AS2	ENST00000654154.2	n.533+4778A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75950 AN: 151966 Hom.: 19122 Cov.: 33

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.500 AC: 76009 AN: 152084 Hom.: 19135 Cov.: 33 AF XY: 0.500 AC XY: 37184 AN XY: 74352

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.527

Alfa AF: 0.471 Hom.: 11778

Bravo AF: 0.506

Asia WGS AF: 0.417 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.27
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1107366; hg19: chr3-125904165;