9-73067764-T-C

Variant names:

• chr9-73067764-T-C
• rs1961830
• ENST00000419959.5:c.-15+12603A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000419959.5(ALDH1A1):​c.-15+12603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,392 control chromosomes in the GnomAD database, including 25,124 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 0.57 (25124 hom., cov: 29)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000419959.5	c.-15+12603A>G		intron_variant	Intron 1 of 7	5		ENSP00000388026.1
ALDH1A1	ENST00000493311.1	n.29+12603A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86547 AN: 151274 Hom.: 25098 Cov.: 29

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.572 AC: 86620 AN: 151392 Hom.: 25124 Cov.: 29 AF XY: 0.575 AC XY: 42513 AN XY: 73922

African (AFR) AF: 0.496 AC: 20409 AN: 41156

American (AMR) AF: 0.604 AC: 9197 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2120 AN: 5140

South Asian (SAS) AF: 0.541 AC: 2574 AN: 4754

European-Finnish (FIN) AF: 0.686 AC: 7196 AN: 10484

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41425 AN: 67872

Other (OTH) AF: 0.580 AC: 1214 AN: 2094

Alfa AF: 0.588 Hom.: 74718

Bravo AF: 0.562

Asia WGS AF: 0.476 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.80
PhyloP100		-0.71

Splicing

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

Other links and lift over

dbSNP: rs1961830; hg19: chr9-75682680;