9-72932696-T-C

Variant names:

• chr9-72932696-T-C
• rs348463
• NM_000689.5:c.172-1677A>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.172-1677A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,122 control chromosomes in the GnomAD database, including 6,534 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 0.29 (6534 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885
• Publications: 9 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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	NM_000689.5	MANE Select	c.172-1677A>G		intron	N/A	NP_000680.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.172-1677A>G		intron	N/A	ENSP00000297785.3
	ALDH1A1	ENST00000419959.5	TSL:5	c.172-1677A>G		intron	N/A	ENSP00000388026.1
	ALDH1A1	ENST00000376939.5	TSL:5	c.172-1677A>G		intron	N/A	ENSP00000366138.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44063 AN: 152004 Hom.: 6533 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.290 AC: 44087 AN: 152122 Hom.: 6534 Cov.: 32 AF XY: 0.288 AC XY: 21414 AN XY: 74372

African (AFR) AF: 0.295 AC: 12239 AN: 41504

American (AMR) AF: 0.333 AC: 5086 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3466

East Asian (EAS) AF: 0.510 AC: 2638 AN: 5172

South Asian (SAS) AF: 0.288 AC: 1392 AN: 4828

European-Finnish (FIN) AF: 0.210 AC: 2219 AN: 10586

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18677 AN: 67984

Other (OTH) AF: 0.290 AC: 614 AN: 2114

Alfa AF: 0.288 Hom.: 9553

Bravo AF: 0.302

Asia WGS AF: 0.402 AC: 1395 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.89
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: rs348463; hg19: chr9-75547612;