9-72927026-G-T

Variant summary

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

The NM_000689.5(ALDH1A1):c.504+90C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 911,920 control chromosomes in the GnomAD database, including 109,853 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 0.43 (15079 hom., cov: 32)
  • Exomes 𝑓: 0.50 (94774 hom.)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A1	NM_000689.5	c.504+90C>A		intron_variant		ENST00000297785.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.504+90C>A		intron_variant		1	NM_000689.5	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64934 AN: 151922 Hom.: 15071 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.495 AC: 376180 AN: 759880 Hom.: 94774 Cov.: 10 AF XY: 0.495 AC XY: 194181 AN XY: 392250

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.427 AC: 64985 AN: 152040 Hom.: 15079 Cov.: 32 AF XY: 0.433 AC XY: 32185 AN XY: 74332

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.434

Alfa AF: 0.472 Hom.: 15814

Bravo AF: 0.410

Asia WGS AF: 0.419 AC: 1456 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.6
Dann	Benign	0.57

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: rs2303317; hg19: chr9-75541942; COSMIC: COSV52789858;