rs348458

Variant names:

• chr9-72914972-C-T
• rs348458
• NM_000689.5:c.1035+1948G>A

Variant summary

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

The NM_000689.5(ALDH1A1):​c.1035+1948G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,714 control chromosomes in the GnomAD database, including 14,711 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 0.44 (14711 hom., cov: 31)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1035+1948G>A		intron_variant	Intron 9 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1035+1948G>A		intron_variant	Intron 9 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66595 AN: 151594 Hom.: 14710 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.439 AC: 66622 AN: 151714 Hom.: 14711 Cov.: 31 AF XY: 0.436 AC XY: 32294 AN XY: 74134

African (AFR) AF: 0.445 AC: 18400 AN: 41328

American (AMR) AF: 0.447 AC: 6816 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2683 AN: 5148

South Asian (SAS) AF: 0.350 AC: 1680 AN: 4804

European-Finnish (FIN) AF: 0.414 AC: 4347 AN: 10508

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29958 AN: 67900

Other (OTH) AF: 0.448 AC: 945 AN: 2108

Alfa AF: 0.440 Hom.: 22373

Bravo AF: 0.447

Asia WGS AF: 0.467 AC: 1622 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.40
PhyloP100		-2.8
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: rs348458; hg19: chr9-75529888;