rs348471

Variant names:

• chr9-72905059-G-A
• rs348471
• NM_000689.5:c.1433+899C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-72905059-G-A
• chr9-72905059-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000689.5(ALDH1A1):​c.1433+899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,790 control chromosomes in the GnomAD database, including 19,495 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 0.51 (19495 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 12 publications found

Genes affected

ALDH1A1 (HGNC:402): (aldehyde dehydrogenase 1 family member A1) The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1433+899C>T		intron_variant	Intron 12 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1433+899C>T		intron_variant	Intron 12 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76890 AN: 151674 Hom.: 19485 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.507 AC: 76930 AN: 151790 Hom.: 19495 Cov.: 32 AF XY: 0.507 AC XY: 37568 AN XY: 74168

African (AFR) AF: 0.513 AC: 21239 AN: 41428

American (AMR) AF: 0.550 AC: 8382 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1482 AN: 3464

East Asian (EAS) AF: 0.521 AC: 2685 AN: 5156

South Asian (SAS) AF: 0.409 AC: 1966 AN: 4812

European-Finnish (FIN) AF: 0.508 AC: 5352 AN: 10540

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34162 AN: 67844

Other (OTH) AF: 0.522 AC: 1100 AN: 2106

Alfa AF: 0.504 Hom.: 75036

Bravo AF: 0.511

Asia WGS AF: 0.512 AC: 1780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.37
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs348471; hg19: chr9-75519975;