9-72906144-A-G

Variant names:

• chr9-72906144-A-G
• rs348472
• NM_000689.5:c.1359-112T>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.1359-112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 687,852 control chromosomes in the GnomAD database, including 294,386 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 0.86 (57835 hom., cov: 30)
  • Exomes 𝑓: 0.94 (236551 hom.)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 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.1359-112T>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.1359-112T>C		intron	N/A	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130908 AN: 151974 Hom.: 57818 Cov.: 30

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.938 AC: 502333 AN: 535760 Hom.: 236551 AF XY: 0.935 AC XY: 265679 AN XY: 284044

African (AFR) AF: 0.652 AC: 8685 AN: 13312

American (AMR) AF: 0.945 AC: 17606 AN: 18640

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 12823 AN: 15354

East Asian (EAS) AF: 0.993 AC: 30312 AN: 30536

South Asian (SAS) AF: 0.883 AC: 37492 AN: 42470

European-Finnish (FIN) AF: 0.976 AC: 43672 AN: 44754

Middle Eastern (MID) AF: 0.894 AC: 3347 AN: 3744

European-Non Finnish (NFE) AF: 0.952 AC: 322413 AN: 338532

Other (OTH) AF: 0.914 AC: 25983 AN: 28418

GnomAD4 genome AF: 0.861 AC: 130976 AN: 152092 Hom.: 57835 Cov.: 30 AF XY: 0.865 AC XY: 64274 AN XY: 74344

African (AFR) AF: 0.640 AC: 26522 AN: 41448

American (AMR) AF: 0.932 AC: 14233 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2866 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5127 AN: 5170

South Asian (SAS) AF: 0.893 AC: 4306 AN: 4824

European-Finnish (FIN) AF: 0.975 AC: 10344 AN: 10604

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64588 AN: 67992

Other (OTH) AF: 0.887 AC: 1869 AN: 2108

Alfa AF: 0.924 Hom.: 115098

Bravo AF: 0.849

Asia WGS AF: 0.924 AC: 3212 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		-0.39
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: rs348472; hg19: chr9-75521060;