chr9-73066055-A-G

Variant names:

• chr9-73066055-A-G
• rs13292677
• ENST00000419959.5:c.-15+14312T>C

Variant summary

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

The ENST00000419959.5(ALDH1A1):​c.-15+14312T>C 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 152,006 control chromosomes in the GnomAD database, including 25,245 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 (25245 hom., cov: 32)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 2 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=-0.9).
• 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+14312T>C		intron_variant	Intron 1 of 7	5		ENSP00000388026.1
ALDH1A1	ENST00000493311.1	n.30-11821T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86868 AN: 151884 Hom.: 25219 Cov.: 32

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: 0.538

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.572 AC: 86942 AN: 152006 Hom.: 25245 Cov.: 32 AF XY: 0.575 AC XY: 42713 AN XY: 74296

African (AFR) AF: 0.496 AC: 20566 AN: 41432

American (AMR) AF: 0.604 AC: 9221 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2123 AN: 5152

South Asian (SAS) AF: 0.540 AC: 2592 AN: 4804

European-Finnish (FIN) AF: 0.686 AC: 7254 AN: 10580

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

European-Non Finnish (NFE) AF: 0.610 AC: 41471 AN: 67978

Other (OTH) AF: 0.581 AC: 1227 AN: 2112

Alfa AF: 0.594 Hom.: 15775

Bravo AF: 0.563

Asia WGS AF: 0.477 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs13292677; hg19: chr9-75680971;