chr9-72907919-A-C

Variant names:

• chr9-72907919-A-C
• rs17058224
• NM_000689.5:c.1358+1683T>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.1358+1683T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,302 control chromosomes in the GnomAD database, including 548 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 0.073 (548 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 3 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000689.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	NM_000689.5	MANE Select	c.1358+1683T>G		intron	N/A	NP_000680.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.1358+1683T>G		intron	N/A	ENSP00000297785.3	P00352
	ALDH1A1	ENST00000856212.1		c.1448+1683T>G		intron	N/A	ENSP00000526271.1
	ALDH1A1	ENST00000966555.1		c.1427+1683T>G		intron	N/A	ENSP00000636614.1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11053 AN: 152184 Hom.: 548 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.00826

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0736

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

GnomAD4 genome AF: 0.0726 AC: 11063 AN: 152302 Hom.: 548 Cov.: 32 AF XY: 0.0712 AC XY: 5306 AN XY: 74494

African (AFR) AF: 0.130 AC: 5391 AN: 41550

American (AMR) AF: 0.0442 AC: 676 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3472

East Asian (EAS) AF: 0.00828 AC: 43 AN: 5194

South Asian (SAS) AF: 0.105 AC: 508 AN: 4822

European-Finnish (FIN) AF: 0.0244 AC: 259 AN: 10626

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0490 AC: 3334 AN: 68014

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0586 Hom.: 932

Bravo AF: 0.0743

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.9
DANN	Benign	0.74
PhyloP100		0.065
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: rs17058224; hg19: chr9-75522835;