rs722921

Positions:

• chr9-72929383-T-A
• chr9-72929383-T-G

Variant summary

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

The NM_000689.5(ALDH1A1):​c.313-362A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,118 control chromosomes in the GnomAD database, including 14,605 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 0.41 (14605 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.313-362A>T		intron_variant		ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.313-362A>T		intron_variant		1	NM_000689.5	ENSP00000297785	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62772 AN: 152000 Hom.: 14601 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.413 AC: 62806 AN: 152118 Hom.: 14605 Cov.: 32 AF XY: 0.419 AC XY: 31145 AN XY: 74382

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.426

Alfa AF: 0.315 Hom.: 913

Bravo AF: 0.394

Asia WGS AF: 0.416 AC: 1446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.98
DANN	Benign	0.86

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: rs722921; hg19: chr9-75544299;