9-72919844-T-G

Variant names:

• chr9-72919844-T-G
• rs348460
• NM_000689.5:c.748-1022A>C

Variant summary

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

The NM_000689.5(ALDH1A1):​c.748-1022A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,264 control chromosomes in the GnomAD database, including 64,496 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 0.92 (64496 hom., cov: 33)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 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.748-1022A>C		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.748-1022A>C		intron	N/A	ENSP00000297785.3
	ALDH1A1	ENST00000376939.5	TSL:5	c.678-2787A>C		intron	N/A	ENSP00000366138.1

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139859 AN: 152146 Hom.: 64451 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.919 AC: 139959 AN: 152264 Hom.: 64496 Cov.: 33 AF XY: 0.920 AC XY: 68446 AN XY: 74438

African (AFR) AF: 0.862 AC: 35820 AN: 41534

American (AMR) AF: 0.949 AC: 14528 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2828 AN: 3472

East Asian (EAS) AF: 0.978 AC: 5056 AN: 5170

South Asian (SAS) AF: 0.851 AC: 4103 AN: 4824

European-Finnish (FIN) AF: 0.965 AC: 10240 AN: 10616

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64300 AN: 68024

Other (OTH) AF: 0.922 AC: 1952 AN: 2116

Alfa AF: 0.934 Hom.: 181879

Bravo AF: 0.917

Asia WGS AF: 0.917 AC: 3189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.43
PhyloP100		-1.1
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: rs348460; hg19: chr9-75534760;