rs348472

Positions:

• chr9-72906144-A-G
• chr9-72906144-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000297785.8(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 ENST00000297785.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1359-112T>C		intron_variant		ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1359-112T>C		intron_variant		1	NM_000689.5	ENSP00000297785	P1

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

Gnomad4 AFR exome AF: 0.652

Gnomad4 AMR exome AF: 0.945

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.993

Gnomad4 SAS exome AF: 0.883

Gnomad4 FIN exome AF: 0.976

Gnomad4 NFE exome AF: 0.952

Gnomad4 OTH exome AF: 0.914

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

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.887

Alfa AF: 0.931 Hom.: 85114

Bravo AF: 0.849

Asia WGS AF: 0.924 AC: 3212 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs348472; hg19: chr9-75521060;