rs2249978

chr9-73012182-A-Gchr9-73012182-A-T

Variant summary

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

The ENST00000419959.5(ALDH1A1):c.-14-59168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,970 control chromosomes in the GnomAD database, including 27,548 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 0.58 (27548 hom., cov: 32)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000419959.5	c.-14-59168T>C		intron_variant		5
ALDH1A1	ENST00000446946.1	c.-15+26359T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88457 AN: 151852 Hom.: 27540 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.582 AC: 88500 AN: 151970 Hom.: 27548 Cov.: 32 AF XY: 0.586 AC XY: 43565 AN XY: 74282

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.615

Alfa AF: 0.617 Hom.: 3586

Bravo AF: 0.558

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	14
Dann	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2249978; hg19: chr9-75627098;