rs8187981

Variant names:

• chr9-72907022-T-C
• rs8187981
• NM_000689.5:c.1359-990A>G

Variant summary

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

The NM_000689.5(ALDH1A1):​c.1359-990A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,866 control chromosomes in the GnomAD database, including 14,831 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 0.42 (14831 hom., cov: 31)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1359-990A>G		intron_variant	Intron 11 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1359-990A>G		intron_variant	Intron 11 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64507 AN: 151748 Hom.: 14819 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.425 AC: 64536 AN: 151866 Hom.: 14831 Cov.: 31 AF XY: 0.429 AC XY: 31797 AN XY: 74194

African (AFR) AF: 0.235 AC: 9722 AN: 41436

American (AMR) AF: 0.487 AC: 7424 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1977 AN: 3464

East Asian (EAS) AF: 0.442 AC: 2269 AN: 5132

South Asian (SAS) AF: 0.583 AC: 2810 AN: 4820

European-Finnish (FIN) AF: 0.494 AC: 5210 AN: 10546

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33573 AN: 67914

Other (OTH) AF: 0.443 AC: 934 AN: 2108

Alfa AF: 0.481 Hom.: 20098

Bravo AF: 0.413

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.84
PhyloP100		1.7
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: rs8187981; hg19: chr9-75521938;