9-72932253-G-C

Variant names:

• chr9-72932253-G-C
• rs348462
• NM_000689.5:c.172-1234C>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.172-1234C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,902 control chromosomes in the GnomAD database, including 11,983 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 0.38 (11983 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.172-1234C>G		intron_variant	Intron 2 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.172-1234C>G		intron_variant	Intron 2 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57804 AN: 151784 Hom.: 11975 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.381 AC: 57857 AN: 151902 Hom.: 11983 Cov.: 32 AF XY: 0.377 AC XY: 27973 AN XY: 74230

African (AFR) AF: 0.541 AC: 22412 AN: 41422

American (AMR) AF: 0.380 AC: 5791 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3468

East Asian (EAS) AF: 0.519 AC: 2676 AN: 5160

South Asian (SAS) AF: 0.355 AC: 1706 AN: 4808

European-Finnish (FIN) AF: 0.230 AC: 2428 AN: 10546

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20305 AN: 67930

Other (OTH) AF: 0.369 AC: 779 AN: 2112

Alfa AF: 0.330 Hom.: 1189

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.40
PhyloP100		-1.2
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: rs348462; hg19: chr9-75547169;